<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01684215</url>
  </required_header>
  <id_info>
    <org_study_id>A5481010</org_study_id>
    <nct_id>NCT01684215</nct_id>
  </id_info>
  <brief_title>A Study Of Oral Palbociclib (PD-0332991), A CDK4/6 Inhibitor, As Single Agent In Japanese Patients With Advanced Solid Tumors Or In Combination With Letrozole For The First-Line Treatment Of Postmenopausal Japanese Patients With ER (+) HER2 (-) Advanced Breast Cancer</brief_title>
  <official_title>A PHASE 1/2 STUDY OF THE EFFICACY, SAFETY, AND PHARMACOKINETICS OF ORAL PD-0332991, A CYCLIN-DEPENDENT KINASE 4 AND 6 (CDK4/6) INHIBITOR, AS SINGLE AGENT IN JAPANESE PATIENTS WITH ADVANCED SOLID TUMORS OR IN COMBINATION WITH LETROZOLE FOR THE FIRST-LINE TREATMENT OF POSTMENOPAUSAL JAPANESE PATIENTS WITH ER (+) HER2 (-) ADVANCED BREAST CANCER</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pfizer</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is comprised of two portions: a Phase 1 portion and a Phase 2 portion. The Phase 1&#xD;
      portion is a single-country, non-randomized, open label, clinical trial which will evaluate&#xD;
      the safety, tolerability, preliminary efficacy, and PK profile of PD-0332991 as a single&#xD;
      agent in Japanese patients with advanced solid tumors, and PD-0332991 in combination with&#xD;
      letrozole in the first-line treatment of Japanese patients with ER(+) HER2(-) ABC. The Phase&#xD;
      2 portion is a single-country, non-randomized, open-label, single-cohort, multi-center&#xD;
      clinical trial to evaluate the efficacy and safety of PD-0332991 in combination with&#xD;
      letrozole for the first-line treatment of postmenopausal Japanese patients with ER(+) HER2(-)&#xD;
      ABC.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 19, 2012</start_date>
  <completion_date type="Actual">October 25, 2018</completion_date>
  <primary_completion_date type="Actual">March 4, 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Dose Limiting Toxicities (DLT): Part 1 Phase 1</measure>
    <time_frame>Lead-in period (Day -7) up to Day 28 (Cycle 1)</time_frame>
    <description>DLT was classified as per common terminology criteria for adverse events (CTCAE) version 4.0 as any of the events occurring during 28 days of Cycle 1,attributed to study drug:grade 4 neutropenia(for a duration of greater than [&gt;]7 days); febrile neutropenia (grade greater than or equal to [&gt;=]3 neutropenia,body temperature &gt;=38.5 degree Celsius);grade &gt;=3 thrombocytopenia with bleeding episode;grade 4 thrombocytopenia;grade &gt;=3 non-hematologic toxicity except grade 3 or more nausea, vomiting,electrolyte abnormality(if controllable by therapy);grade 3 QTc prolongation(&gt;500 millisecond [msec])persist after correction of reversible cause such as electrolyte abnormalities or hypoxia. Lack of hematologic recovery (platelets less than [&lt;]50,000/microliter [mcL],absolute neutrophil count &lt;1,000/mcL,hemoglobin &lt;8.0 gram/deciliter [g/dL]) or prolonged non hematologic toxicities that delays initiation of next dose by &gt;7 days;receipt of &lt;75 percent of planned dose in first cycle due to toxicity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2 Phase 1</measure>
    <time_frame>Baseline (Day 1) up to 28 days after last dose of study drug (up to 1673 days)</time_frame>
    <description>A treatment related AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.&#xD;
Relatedness was judged by investigator. AEs included both serious and non-serious adverse events.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Treatment-Emergent Adverse Events (TEAEs) By Severity: Part 2 Phase 1</measure>
    <time_frame>Baseline (Day 1) up to 28 days after last dose of study drug (up to 1673 days)</time_frame>
    <description>AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment but increased in National Cancer Institute (NCI) CTCAE grade during study treatment period. AE severity was defined to be the maximum toxicity grade of the TEAEs experienced by the participants during the study. AE was assessed according to severity as: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants With 1 Year Progression Free Survival (PFS): Phase 2</measure>
    <time_frame>From initiation of treatment up to 12 months</time_frame>
    <description>PFS was defined as the time from first dose of study treatment to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD, whichever occurred first. PD was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.1-year PFS was defined as the percentage of participants without PFS events (PD or death due to any cause) at 12 months based on the Kaplan-Meier estimate. Percentage of participants with 1-year PFS with 90% confidence interval (CI) were reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Phase 1 (Part 1) and Phase 2</measure>
    <time_frame>Part 1 Phase 1: Lead-in period (Day -7) up to 28 days after last dose of study drug (up to 308 days), Phase 2: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1526 days)</time_frame>
    <description>A treatment related AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.&#xD;
Relatedness was judged by investigator. AEs included both serious and non-serious adverse events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-Emergent Adverse Events (AEs) By Severity: Phase 1 (Part 1) and Phase 2</measure>
    <time_frame>Part 1 Phase 1: Lead-in period (Day -7) up to 28 days after last dose of study drug (up to 308 days), Phase 2: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1526 days)</time_frame>
    <description>AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment but increased in NCI CTCAE version 4.0 grade during study treatment period. AE severity was defined to be the maximum toxicity grade of the TEAEs experienced by the participants during the study. AE was assessed according to severity as: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Significant Laboratory Abnormalities</measure>
    <time_frame>Part 1 Phase 1: Lead-in period (Day -7) up to 308 days; Part 2 Phase 1: Baseline (Day 1) up to 1673 days; Phase 2: Baseline (Day 1) up to 1526 days</time_frame>
    <description>Abnormality criteria: hemoglobin: &lt;0.8*lower limit of normal [LLN], platelets: &lt;0.5*LLN or &gt;1.75*upper limit of normal [ULN], leukocytes: &lt;0.6*LLN or &gt;1.5*ULN, lymphocytes, total neutrophils: &lt;0.8*LLN or &gt;1.2*ULN, basophils, eosinophil,monocytes: &gt;1.2*ULN); aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase (GT): &gt;0.3*ULN, total protein, albumin: &lt;0.8*LLN or &gt;1.2*ULN, total bilirubin, direct bilirubin: &gt;1.5*ULN; blood urea nitrogen, creatinine: &gt;1.3*ULN, uric acid: &gt;1.2*ULN; sodium: &lt;0.95*LLN or &gt;1.05*ULN, potassium, chloride, calcium, magnesium: &lt;0.9*LLN or &gt;1.1*ULN, phosphate: &lt;0.8*LLN or &gt;1.2*ULN; creatine kinase: &gt;2.0*ULN, glucose fasting: &lt;0.6*LLN or &gt;1.5*ULN, glycosylated haemoglobin: &gt;1.3*ULN;urinalysis dipstick (urine protein, urine blood &gt;=1); urine protein 24 hour: &gt;1.1*ULN; coagulation Activated partial thromboplastin time [APTT], Prothrombin, prothrombin international ratio: &gt;1.1*ULN.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration Time Curve Over Dosing Interval (AUCtau) of PD-0332991 Following Multiple Dose: Part 1 Phase 1</measure>
    <time_frame>Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
    <description>AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCtau Dose Normalized to 125 Milligram (mg) of PD-0332991 Following Multiple Dose: Part 1 Phase 1</measure>
    <time_frame>Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
    <description>AUCtau Dose Normalized to 125 mg is area under the plasma concentration-time curve over dosing interval dose normalized to 125 mg which is calculated by log-linear trapezoidal method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From 0 to Time 24 Hours (AUC24) of PD-0332991 Following Single Dose: Part 1 Phase 1</measure>
    <time_frame>Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12 and 24 hours post-dose in Lead-in period (Day -7)</time_frame>
    <description>AUC24 is area under the plasma concentration-time curve from 0 to time 24 hours which is calculated by log-linear trapezoidal method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC24 Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1</measure>
    <time_frame>Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12 and 24 hours post-dose in Lead-in period (Day -7)</time_frame>
    <description>AUC24 Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to time 24 hours dose normalized to 125 mg which is calculated by log-linear trapezoidal method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of PD-0332991 Following Single Dose: Part 1 Phase 1</measure>
    <time_frame>Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)</time_frame>
    <description>AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCinf Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1</measure>
    <time_frame>Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)</time_frame>
    <description>AUCinf Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to infinity dose normalized to 125 mg which is calculated by log-linear trapezoidal method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From 0 to Time of Last Measurable Concentration (AUClast) of PD-0332991 Following Single Dose: Part 1 Phase 1</measure>
    <time_frame>Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)</time_frame>
    <description>AUClast is area under the plasma concentration-time curve from 0 to time of last measurable concentration which is calculated by log-linear trapezoidal method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUClast Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1</measure>
    <time_frame>Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)</time_frame>
    <description>AUClast Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to time of last measurable concentration dose normalized to 125 mg which is calculated by log-linear trapezoidal method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Oral Clearance of PD-0332991: Part 1 Phase 1</measure>
    <time_frame>Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
    <description>Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by AUCinf. AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) Of PD-0332991: Part 1 Phase 1</measure>
    <time_frame>Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
    <description>Cmax is maximum plasma concentration which is observed directly from the actual time-concentration data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax Dose Normalized to 125 mg of PD-0332991: Part 1 Phase 1</measure>
    <time_frame>Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
    <description>Cmax Dose Normalized to 125 mg is maximum plasma concentration dose normalized to 125 mg which is observed directly from the actual time-concentration data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pre-dose Plasma Concentration (Ctrough) of PD-0332991 Following Multiple Dose: Part 1 Phase 1</measure>
    <time_frame>Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
    <description>Ctrough is pre-dose concentration during multiple dosing which is observed directly from the actual time-concentration data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation Ratio (Rac) of PD-0332991 Following Multiple Dose: Part 1 Phase 1</measure>
    <time_frame>Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
    <description>Rac is the ratio of AUCtau (after multiple doses) to AUCtau (after single dose). AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Linearity (Rss) of PD-0332991 Following Multiple Dose: Part 1 Phase 1</measure>
    <time_frame>Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
    <description>Rss is the ratio of AUCtau (after multiple doses) to AUCinf (after single dose). AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method. AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991: Part 1 Phase 1</measure>
    <time_frame>Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
    <description>Tmax is time at which maximum plasma concentration (Cmax) was observed. It was observed directly from data as time of first occurrence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Half-Life (t1/2) of PD-0332991: Part 1 Phase 1</measure>
    <time_frame>Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
    <description>t1/2 is terminal elimination half-life which is calculated by loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of Distribution (Vz/F) of PD-0332991 Following Single Dose: Part 1 Phase 1</measure>
    <time_frame>Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)</time_frame>
    <description>Vz/F is apparent volume of distribution estimated from terminal phase, which is calculated as CL/F/kel. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method (AUCinf). kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration Time Curve Over Dosing Interval (AUCtau) of PD-0332991: Phase 2</measure>
    <time_frame>0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15</time_frame>
    <description>AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Oral Clearance of PD-0332991: Phase 2</measure>
    <time_frame>0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15</time_frame>
    <description>Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by AUCtau. AUCtau is the area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) Of PD-0332991: Phase 2</measure>
    <time_frame>0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15</time_frame>
    <description>Cmax is maximum plasma concentration which is observed directly from the actual time-concentration data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991: Phase 2</measure>
    <time_frame>0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15</time_frame>
    <description>Tmax is time at which maximum plasma concentration (Cmax) was observed. It was observed directly from data as time of first occurrence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pre-dose Plasma Concentration (Ctrough) of PD-0332991: Phase 2</measure>
    <time_frame>0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15</time_frame>
    <description>Ctrough is pre-dose concentration during multiple dosing which is observed directly from the actual time-concentration data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Objective Response: Phase 1</measure>
    <time_frame>From initiation of treatment up to disease progression (up to 30 months)</time_frame>
    <description>Objective response (OR) was defined as a complete response (CR) or partial response (PR) according to the RECIST version 1.1 recorded from first dose of study treatment until disease progression or death due to any cause. CR was defined as disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis &lt;10 millimeter [mm]). PR was defined as a &gt;=30 percent decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Percentage of participants with objective response (who achieved CR or PR) were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Objective Response: Phase 2</measure>
    <time_frame>From initiation of treatment up to disease progression (up to 1526 days)</time_frame>
    <description>Objective response was defined as a complete response (CR) or partial response (PR) according to the RECIST version 1.1 recorded from first dose of study treatment until disease progression or death due to any cause. PD was defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. CR was defined as disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis &lt;10 mm). PR was defined as a &gt;=30% decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Percentage of participants with objective response (who achieved CR or PR) were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR): Part 2 Phase 1</measure>
    <time_frame>baseline up to 1673 days</time_frame>
    <description>Duration of response was defined as the interval from the first documentation of objective tumor response in participants with CR (disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis &lt;10 millimeter [mm]) or PR (a &gt;=30 percent decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions) according to RECIST version 1.1 to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR): Phase 2</measure>
    <time_frame>From initiation of treatment up to disease progression (up to 1526 days)</time_frame>
    <description>Duration of response was defined as the interval from the first documentation of objective tumor response in participants with CR (disappearance of all target lesions with the exception of nodal disease, all target nodes reduced to normal size (short axis &lt;10 mm) or PR (a &gt;=30 % decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions) according to RECIST version 1.1 to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. PD was defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS): Part 2 Phase 1</measure>
    <time_frame>baseline up to 1673 days</time_frame>
    <description>PFS was defined as the time from first dose of study treatment to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PD was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Disease Control (DC): Phase 2</measure>
    <time_frame>From initiation of treatment up to disease progression (up to 1526 days)</time_frame>
    <description>DC: CR, PR or stable disease (SD) for &gt;=24 weeks according to RECIST version (v)1.1 recorded in time period between first dose of study treatment and disease progression or death to any cause. CR: disappearance of all target lesions with exception of nodal disease. All target nodes reduced to normal size (short axis &lt;10 mm). PR: &gt;=30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions. SD was defined as not achieving an OR with confirmed CR or PR according to RECIST v1.1, as determined by investigators, relative to response evaluable population, but remained stable for at least 24 weeks after first dose, then best overall response for such a participant was considered as stable disease. PD was defined using RECIST v1.1 as a 20% increase in sum of longest diameter of target lesions, or a measurable increase in a non-target lesion, or appearance of new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS): Phase 2</measure>
    <time_frame>From initiation of treatment up to follow-up period (up to 1526 days)</time_frame>
    <description>Overall survival was defined as the time from first dose of study treatment to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. OS was estimated with Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment</measure>
    <time_frame>Baseline (Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, End of treatment (up to 1526 days)</time_frame>
    <description>The functional assessment of cancer therapy (FACT) is a modular approach to assess participant's health-related quality of life. FACT-B total score was derived from the sum of these 5 sub-scale scores: physical well-being, social/family well-being and functional well-being (all 3 sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life), emotional well-being (consists of 6 items and ranging from 0 to 24, where higher scores indicating better quality of life, and a breast cancer subscale (consists of 9 items and ranging from 0 to 36, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. FACT-B total score range was of 0 (not at all good) to 144 (very well), where higher scores indicating better quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment</measure>
    <time_frame>Baseline (Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, End of treatment (up to 1526 days)</time_frame>
    <description>FACT is a modular approach to assess participant's health-related quality of life. FACT-G total score was derived from the sum of these 4 sub-scale scores: physical well-being, social/family well-being and functional well-being (all 3 sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life), emotional well-being (consists of 6 items and ranging from 0 to 24, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. FACT-G total score range was of 0 (not at all good) to 108 (very well), where higher scores indicating better quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Trial Outcome Index (TOI): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment</measure>
    <time_frame>Baseline (Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, End of treatment (up to 1526 days)</time_frame>
    <description>FACT is a modular approach to assess participant's health-related quality of life. TOI total score was derived from the sum of the 3 sub-scale scores: physical well-being, functional well-being (both sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life) and breast cancer subscale (consists of 9 items and ranging from 0 to 36, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. TOI total score range was of 0 (not at all good) to 92 (very well), where higher scores indicating better quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of Tumor Tissue Biomarker- Ki67: Phase 2</measure>
    <time_frame>Baseline (Day 1)</time_frame>
    <description>Tumor tissue biomarker, Ki67 was analyzed to investigate possible associations with resistance or sensitivity to treatment with study drugs and was selected based on its known relevance to mechanisms involved in cell cycle regulation. Number of participants with less than or equal to and greater than 20 percent of Ki67 tumor tissue biomarker were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of Tumor Tissue Biomarkers- Estrogen Receptor (ER) H-Score, Retinoblastoma (Rb) H-Score, B-cell Lymphoma-1 (BCL-1) H-Score, P16 H-Score: Phase 2</measure>
    <time_frame>Baseline (Day 1)</time_frame>
    <description>Tumor tissue biomarkers ER, Rb, BCL-1 and P16 were analyzed to investigate possible associations with resistance or sensitivity to treatment with study drugs and were selected based on their known relevance to mechanisms involved in cell cycle regulation. Number of participants with positive ER (H-Score), Rb (H-Score), BCL-1 (H-Score) and P16 (H-Score) tumor tissue biomarkers were reported. The H-score is a method of assessing the extent of nuclear immunoreactivity, applicable to steroid receptors.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">61</enrollment>
  <condition>Neoplasms</condition>
  <condition>Breast Neoplasms</condition>
  <arm_group>
    <arm_group_label>Single-agent PD-0332991</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase 1 Part 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PD-0332991 in combination with letrozole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase 1 Part 2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PD-0332991 with letrozole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase 2</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PD-0332991</intervention_name>
    <description>PD-0332991 (100 mg or 125 mg) will be orally administered once a day for 3 weeks followed by 1 week off treatment, in the morning on an empty stomach. Dose reduction of PD-0332991 by one (100 mg) or two (75 mg) dose level is permitted depending on treatment related toxicity.</description>
    <arm_group_label>Single-agent PD-0332991</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PD-0332991</intervention_name>
    <description>PD-0332991, 125 mg, will be orally administered with food once a day for 3 weeks followed by 1 week off treatment. PD-0332991 will be administered once a day together with letrozole. Dose reduction of PD-0332991 by one (100 mg) or two (75 mg) dose level is permitted depending on treatment related toxicity.</description>
    <arm_group_label>PD-0332991 in combination with letrozole</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>letrozole</intervention_name>
    <description>Letrozole, 2.5 mg, will be orally administered once a day in continuous daily dosing together with PD-0332991. Dose reduction of letrozole is not permitted, but dosing interruptions for letrozole-related toxicity are allowed as per investigator's medical judgement.</description>
    <arm_group_label>PD-0332991 in combination with letrozole</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PD-0332991</intervention_name>
    <description>PD-0332991, 125 mg, will be orally administered with food once a day for 3 weeks followed by 1 week off treatment. PD-0332991 will be administered once a day together with letrozole. Dose reduction of PD-0332991 by one (100 mg) or two (75 mg) dose level is permitted depending on treatment related toxicity.</description>
    <arm_group_label>PD-0332991 with letrozole</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>letrozole</intervention_name>
    <description>Letrozole, 2.5 mg, will be orally administered once a day in continuous daily dosing together with PD-0332991. Dose reduction of letrozole is not permitted, but dosing interruptions for letrozole-related toxicity are allowed as per investigator's medical judgement.</description>
    <arm_group_label>PD-0332991 with letrozole</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Phase 1&#xD;
&#xD;
          -  In Part 1, advanced solid tumor (except SCLC or retinoblastoma) proven histologically&#xD;
             or cytologically at original diagnosis, that is refractory to standard therapy or for&#xD;
             whom no standard of care therapy is available.&#xD;
&#xD;
          -  In Part 2 and Phase 2, post menopausal women with proven diagnosis of ER-positive,&#xD;
             HER2-negative adenocarcinoma of the breast with evidence of locoregionally recurrent&#xD;
             or metastatic disease (including bone only disease) not amenable to resection or&#xD;
             radiation therapy with curative intent and for whom chemotherapy is not clinically&#xD;
             indicated.&#xD;
&#xD;
          -  Adequate blood cell counts, kidney function and liver function and and Eastern&#xD;
             Cooperative Oncology Group [ECOG] score of 0 or 1.&#xD;
&#xD;
          -  Resolved acute effects of any prior therapy to baseline severity or Grade ≤1&#xD;
&#xD;
        Phase 2&#xD;
&#xD;
          -  Adult women (≥ 20 years of age) with proven diagnosis of adenocarcinoma of the breast&#xD;
             with evidence of locoregionally recurrent or metastatic disease not amenable to&#xD;
             resection or radiation therapy with curative intent and for whom chemotherapy is not&#xD;
             clinically indicated.&#xD;
&#xD;
          -  Documentation of histologically or cytologically confirmed diagnosis of ER(+) breast&#xD;
             cancer based on local laboratory results.&#xD;
&#xD;
          -  Adequate blood cell counts, kidney function and liver function and and Eastern&#xD;
             Cooperative Oncology Group [ECOG] score of 0 to 2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Phase 1&#xD;
&#xD;
          -  Active uncontrolled or symptomatic CNS metastases.&#xD;
&#xD;
          -  Uncontrolled infection, unstable or sever intercurrent medical condition, or current&#xD;
             drug or alcohol abuse&#xD;
&#xD;
          -  Active or unstable cardiac disease or history of heart attack within 6 months&#xD;
&#xD;
        Phase 2&#xD;
&#xD;
          -  HER2 positive tumor based on local laboratory results utilizing one of the sponsor&#xD;
             approved assays.&#xD;
&#xD;
          -  Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or&#xD;
             leptomeningeal disease.&#xD;
&#xD;
          -  Prior neoadjuvant or adjuvant treatment with a non steroidal aromatase inhibitor (ie,&#xD;
             anastrozole or letrozole) with disease recurrence while on or within 12 months of&#xD;
             completing treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pfizer CT.gov Call Center</last_name>
    <role>Study Director</role>
    <affiliation>Pfizer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Aichi Cancer Center Hospital</name>
      <address>
        <city>Nagoya</city>
        <state>Aichi</state>
        <zip>464-8681</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital East</name>
      <address>
        <city>Kashiwa</city>
        <state>Chiba</state>
        <zip>277-8577</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Hokkaido Cancer Center</name>
      <address>
        <city>Sapporo</city>
        <state>Hokkaido</state>
        <zip>003-0804</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kumamoto Shinto General Hospital</name>
      <address>
        <city>Kumamoto-city</city>
        <state>Kumamoto</state>
        <zip>862-8655</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saitama Cancer Center</name>
      <address>
        <city>Kita-adachi-gun</city>
        <state>Saitama</state>
        <zip>362-0806</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital</name>
      <address>
        <city>Chuo-Ku</city>
        <state>Tokyo</state>
        <zip>104-0045</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chiba Cancer Center</name>
      <address>
        <city>Chiba</city>
        <zip>260-8717</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Shikoku Cancer Center</name>
      <address>
        <city>Ehime</city>
        <zip>791-0280</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Kyushu Cancer Center</name>
      <address>
        <city>Fukuoka</city>
        <zip>811-1395</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hiroshima City Hiroshima Citizens Hospital</name>
      <address>
        <city>Hiroshima</city>
        <zip>730-8518</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Iwate Medical University Hospital</name>
      <address>
        <city>Iwate</city>
        <zip>020-8505</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hakuaikai Medical Corporation Sagara Hospital</name>
      <address>
        <city>Kagoshima</city>
        <zip>892-0833</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kumamoto University Hospital</name>
      <address>
        <city>Kumamoto</city>
        <zip>860-8556</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kumamoto City Hospital</name>
      <address>
        <city>Kumamoto</city>
        <zip>862-8505</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kyoto University Hospital</name>
      <address>
        <city>Kyoto</city>
        <zip>606-8507</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Osaka National Hospital</name>
      <address>
        <city>Osaka</city>
        <zip>540-0006</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <link>
    <url>https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A5481010&amp;StudyName=A%20Study%20Of%20Oral%20Palbociclib%20%28PD-0332991%29%2C%20A%20CDK4/6%20Inhibitor%2C%20As%20Single%20Agent%20In%20Japanese%20Patients%20With%20Advanced%20Solid%20Tumors%20Or</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>September 10, 2012</study_first_submitted>
  <study_first_submitted_qc>September 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2012</study_first_posted>
  <results_first_submitted>November 9, 2016</results_first_submitted>
  <results_first_submitted_qc>March 21, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 2, 2017</results_first_posted>
  <last_update_submitted>October 28, 2020</last_update_submitted>
  <last_update_submitted_qc>October 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Phase 1/2</keyword>
  <keyword>PD-0332991</keyword>
  <keyword>palbociclib</keyword>
  <keyword>Cyclin Dependent Kinase 4/6 inhibitor</keyword>
  <keyword>Japanese</keyword>
  <keyword>solid tumors</keyword>
  <keyword>breast cancer</keyword>
  <keyword>A5481010</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Letrozole</mesh_term>
    <mesh_term>Palbociclib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.</ipd_description>
    <ipd_url>https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests</ipd_url>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Study comprised of 2 phases: Participants were enrolled to dose escalation cohorts (PD-0332991 100 milligram [mg] and 125 mg) in Phase 1 Part 1, to maximum tolerated dose (MTD) cohort (PD-0332991 125 mg+ Letrozole 2.5 mg) in Phase 1 Part 2 and to expanded cohort (PD-0332991 125 mg and Letrozole 2.5 mg) in Phase 2.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
          <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
        </group>
        <group group_id="P2">
          <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
          <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
        </group>
        <group group_id="P3">
          <title>PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort</title>
          <description>In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
        </group>
        <group group_id="P4">
          <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
          <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Phase 1, Part 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Objective progression or relapse</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Phase 1, Part 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="6">Eligible participants who consented for Phase 1 Part 2.</participants>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Commercial avaliabity of Palbociclib</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Phase 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="43">Eligible participants who consented for Phase 2.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="42"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="43"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study terminated by sponsor</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="30"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Enrolled but not treated</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
      <group_list>
        <group group_id="B1">
          <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
          <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
        </group>
        <group group_id="B2">
          <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
          <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
        </group>
        <group group_id="B3">
          <title>PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort</title>
          <description>In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
        </group>
        <group group_id="B4">
          <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
          <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="42"/>
            <count group_id="B5" value="60"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="26"/>
                    <measurement group_id="B5" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="16"/>
                    <measurement group_id="B5" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="42"/>
                    <measurement group_id="B5" value="55"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Dose Limiting Toxicities (DLT): Part 1 Phase 1</title>
        <description>DLT was classified as per common terminology criteria for adverse events (CTCAE) version 4.0 as any of the events occurring during 28 days of Cycle 1,attributed to study drug:grade 4 neutropenia(for a duration of greater than [&gt;]7 days); febrile neutropenia (grade greater than or equal to [&gt;=]3 neutropenia,body temperature &gt;=38.5 degree Celsius);grade &gt;=3 thrombocytopenia with bleeding episode;grade 4 thrombocytopenia;grade &gt;=3 non-hematologic toxicity except grade 3 or more nausea, vomiting,electrolyte abnormality(if controllable by therapy);grade 3 QTc prolongation(&gt;500 millisecond [msec])persist after correction of reversible cause such as electrolyte abnormalities or hypoxia. Lack of hematologic recovery (platelets less than [&lt;]50,000/microliter [mcL],absolute neutrophil count &lt;1,000/mcL,hemoglobin &lt;8.0 gram/deciliter [g/dL]) or prolonged non hematologic toxicities that delays initiation of next dose by &gt;7 days;receipt of &lt;75 percent of planned dose in first cycle due to toxicity.</description>
        <time_frame>Lead-in period (Day -7) up to Day 28 (Cycle 1)</time_frame>
        <population>DLT analysis set included all participants whom DLTs were evaluable in Part 1 Phase 1.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Dose Limiting Toxicities (DLT): Part 1 Phase 1</title>
          <description>DLT was classified as per common terminology criteria for adverse events (CTCAE) version 4.0 as any of the events occurring during 28 days of Cycle 1,attributed to study drug:grade 4 neutropenia(for a duration of greater than [&gt;]7 days); febrile neutropenia (grade greater than or equal to [&gt;=]3 neutropenia,body temperature &gt;=38.5 degree Celsius);grade &gt;=3 thrombocytopenia with bleeding episode;grade 4 thrombocytopenia;grade &gt;=3 non-hematologic toxicity except grade 3 or more nausea, vomiting,electrolyte abnormality(if controllable by therapy);grade 3 QTc prolongation(&gt;500 millisecond [msec])persist after correction of reversible cause such as electrolyte abnormalities or hypoxia. Lack of hematologic recovery (platelets less than [&lt;]50,000/microliter [mcL],absolute neutrophil count &lt;1,000/mcL,hemoglobin &lt;8.0 gram/deciliter [g/dL]) or prolonged non hematologic toxicities that delays initiation of next dose by &gt;7 days;receipt of &lt;75 percent of planned dose in first cycle due to toxicity.</description>
          <population>DLT analysis set included all participants whom DLTs were evaluable in Part 1 Phase 1.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2 Phase 1</title>
        <description>A treatment related AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.&#xD;
Relatedness was judged by investigator. AEs included both serious and non-serious adverse events.</description>
        <time_frame>Baseline (Day 1) up to 28 days after last dose of study drug (up to 1673 days)</time_frame>
        <population>Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort</title>
            <description>In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2 Phase 1</title>
          <description>A treatment related AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.&#xD;
Relatedness was judged by investigator. AEs included both serious and non-serious adverse events.</description>
          <population>Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Treatment-Emergent Adverse Events (TEAEs) By Severity: Part 2 Phase 1</title>
        <description>AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment but increased in National Cancer Institute (NCI) CTCAE grade during study treatment period. AE severity was defined to be the maximum toxicity grade of the TEAEs experienced by the participants during the study. AE was assessed according to severity as: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE).</description>
        <time_frame>Baseline (Day 1) up to 28 days after last dose of study drug (up to 1673 days)</time_frame>
        <population>Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort</title>
            <description>In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-Emergent Adverse Events (TEAEs) By Severity: Part 2 Phase 1</title>
          <description>AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment but increased in National Cancer Institute (NCI) CTCAE grade during study treatment period. AE severity was defined to be the maximum toxicity grade of the TEAEs experienced by the participants during the study. AE was assessed according to severity as: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE).</description>
          <population>Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With 1 Year Progression Free Survival (PFS): Phase 2</title>
        <description>PFS was defined as the time from first dose of study treatment to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD, whichever occurred first. PD was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.1-year PFS was defined as the percentage of participants without PFS events (PD or death due to any cause) at 12 months based on the Kaplan-Meier estimate. Percentage of participants with 1-year PFS with 90% confidence interval (CI) were reported.</description>
        <time_frame>From initiation of treatment up to 12 months</time_frame>
        <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
            <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With 1 Year Progression Free Survival (PFS): Phase 2</title>
          <description>PFS was defined as the time from first dose of study treatment to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD, whichever occurred first. PD was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.1-year PFS was defined as the percentage of participants without PFS events (PD or death due to any cause) at 12 months based on the Kaplan-Meier estimate. Percentage of participants with 1-year PFS with 90% confidence interval (CI) were reported.</description>
          <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75.6" lower_limit="62.4" upper_limit="84.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Phase 1 (Part 1) and Phase 2</title>
        <description>A treatment related AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.&#xD;
Relatedness was judged by investigator. AEs included both serious and non-serious adverse events.</description>
        <time_frame>Part 1 Phase 1: Lead-in period (Day -7) up to 28 days after last dose of study drug (up to 308 days), Phase 2: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1526 days)</time_frame>
        <population>Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O3">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
            <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Phase 1 (Part 1) and Phase 2</title>
          <description>A treatment related AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.&#xD;
Relatedness was judged by investigator. AEs included both serious and non-serious adverse events.</description>
          <population>Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-Emergent Adverse Events (AEs) By Severity: Phase 1 (Part 1) and Phase 2</title>
        <description>AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment but increased in NCI CTCAE version 4.0 grade during study treatment period. AE severity was defined to be the maximum toxicity grade of the TEAEs experienced by the participants during the study. AE was assessed according to severity as: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE).</description>
        <time_frame>Part 1 Phase 1: Lead-in period (Day -7) up to 28 days after last dose of study drug (up to 308 days), Phase 2: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1526 days)</time_frame>
        <population>Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O3">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
            <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-Emergent Adverse Events (AEs) By Severity: Phase 1 (Part 1) and Phase 2</title>
          <description>AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment but increased in NCI CTCAE version 4.0 grade during study treatment period. AE severity was defined to be the maximum toxicity grade of the TEAEs experienced by the participants during the study. AE was assessed according to severity as: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE).</description>
          <population>Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinically Significant Laboratory Abnormalities</title>
        <description>Abnormality criteria: hemoglobin: &lt;0.8*lower limit of normal [LLN], platelets: &lt;0.5*LLN or &gt;1.75*upper limit of normal [ULN], leukocytes: &lt;0.6*LLN or &gt;1.5*ULN, lymphocytes, total neutrophils: &lt;0.8*LLN or &gt;1.2*ULN, basophils, eosinophil,monocytes: &gt;1.2*ULN); aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase (GT): &gt;0.3*ULN, total protein, albumin: &lt;0.8*LLN or &gt;1.2*ULN, total bilirubin, direct bilirubin: &gt;1.5*ULN; blood urea nitrogen, creatinine: &gt;1.3*ULN, uric acid: &gt;1.2*ULN; sodium: &lt;0.95*LLN or &gt;1.05*ULN, potassium, chloride, calcium, magnesium: &lt;0.9*LLN or &gt;1.1*ULN, phosphate: &lt;0.8*LLN or &gt;1.2*ULN; creatine kinase: &gt;2.0*ULN, glucose fasting: &lt;0.6*LLN or &gt;1.5*ULN, glycosylated haemoglobin: &gt;1.3*ULN;urinalysis dipstick (urine protein, urine blood &gt;=1); urine protein 24 hour: &gt;1.1*ULN; coagulation Activated partial thromboplastin time [APTT], Prothrombin, prothrombin international ratio: &gt;1.1*ULN.</description>
        <time_frame>Part 1 Phase 1: Lead-in period (Day -7) up to 308 days; Part 2 Phase 1: Baseline (Day 1) up to 1673 days; Phase 2: Baseline (Day 1) up to 1526 days</time_frame>
        <population>Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O3">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort</title>
            <description>In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O4">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
            <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Laboratory Abnormalities</title>
          <description>Abnormality criteria: hemoglobin: &lt;0.8*lower limit of normal [LLN], platelets: &lt;0.5*LLN or &gt;1.75*upper limit of normal [ULN], leukocytes: &lt;0.6*LLN or &gt;1.5*ULN, lymphocytes, total neutrophils: &lt;0.8*LLN or &gt;1.2*ULN, basophils, eosinophil,monocytes: &gt;1.2*ULN); aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase (GT): &gt;0.3*ULN, total protein, albumin: &lt;0.8*LLN or &gt;1.2*ULN, total bilirubin, direct bilirubin: &gt;1.5*ULN; blood urea nitrogen, creatinine: &gt;1.3*ULN, uric acid: &gt;1.2*ULN; sodium: &lt;0.95*LLN or &gt;1.05*ULN, potassium, chloride, calcium, magnesium: &lt;0.9*LLN or &gt;1.1*ULN, phosphate: &lt;0.8*LLN or &gt;1.2*ULN; creatine kinase: &gt;2.0*ULN, glucose fasting: &lt;0.6*LLN or &gt;1.5*ULN, glycosylated haemoglobin: &gt;1.3*ULN;urinalysis dipstick (urine protein, urine blood &gt;=1); urine protein 24 hour: &gt;1.1*ULN; coagulation Activated partial thromboplastin time [APTT], Prothrombin, prothrombin international ratio: &gt;1.1*ULN.</description>
          <population>Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="6"/>
                    <measurement group_id="O4" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration Time Curve Over Dosing Interval (AUCtau) of PD-0332991 Following Multiple Dose: Part 1 Phase 1</title>
        <description>AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.</description>
        <time_frame>Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
        <population>Pharmacokinetic (PK) parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Time Curve Over Dosing Interval (AUCtau) of PD-0332991 Following Multiple Dose: Part 1 Phase 1</title>
          <description>AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.</description>
          <population>Pharmacokinetic (PK) parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>nanogram*hour per milliliter (ng*hr/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1276" spread="45"/>
                    <measurement group_id="O2" value="2838" spread="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUCtau Dose Normalized to 125 Milligram (mg) of PD-0332991 Following Multiple Dose: Part 1 Phase 1</title>
        <description>AUCtau Dose Normalized to 125 mg is area under the plasma concentration-time curve over dosing interval dose normalized to 125 mg which is calculated by log-linear trapezoidal method.</description>
        <time_frame>Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>AUCtau Dose Normalized to 125 Milligram (mg) of PD-0332991 Following Multiple Dose: Part 1 Phase 1</title>
          <description>AUCtau Dose Normalized to 125 mg is area under the plasma concentration-time curve over dosing interval dose normalized to 125 mg which is calculated by log-linear trapezoidal method.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>ng*hr/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1595" spread="45"/>
                    <measurement group_id="O2" value="2838" spread="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-Time Curve From 0 to Time 24 Hours (AUC24) of PD-0332991 Following Single Dose: Part 1 Phase 1</title>
        <description>AUC24 is area under the plasma concentration-time curve from 0 to time 24 hours which is calculated by log-linear trapezoidal method.</description>
        <time_frame>Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12 and 24 hours post-dose in Lead-in period (Day -7)</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-Time Curve From 0 to Time 24 Hours (AUC24) of PD-0332991 Following Single Dose: Part 1 Phase 1</title>
          <description>AUC24 is area under the plasma concentration-time curve from 0 to time 24 hours which is calculated by log-linear trapezoidal method.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>ng*hr/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="547.5" spread="19"/>
                    <measurement group_id="O2" value="1322" spread="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC24 Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1</title>
        <description>AUC24 Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to time 24 hours dose normalized to 125 mg which is calculated by log-linear trapezoidal method.</description>
        <time_frame>Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12 and 24 hours post-dose in Lead-in period (Day -7)</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC24 Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1</title>
          <description>AUC24 Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to time 24 hours dose normalized to 125 mg which is calculated by log-linear trapezoidal method.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>ng*hr/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="684.5" spread="19"/>
                    <measurement group_id="O2" value="1322" spread="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of PD-0332991 Following Single Dose: Part 1 Phase 1</title>
        <description>AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.</description>
        <time_frame>Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of PD-0332991 Following Single Dose: Part 1 Phase 1</title>
          <description>AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>ng*hr/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1039" spread="32"/>
                    <measurement group_id="O2" value="2483" spread="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUCinf Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1</title>
        <description>AUCinf Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to infinity dose normalized to 125 mg which is calculated by log-linear trapezoidal method.</description>
        <time_frame>Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>AUCinf Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1</title>
          <description>AUCinf Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to infinity dose normalized to 125 mg which is calculated by log-linear trapezoidal method.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>ng*hr/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1296" spread="32"/>
                    <measurement group_id="O2" value="2483" spread="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-Time Curve From 0 to Time of Last Measurable Concentration (AUClast) of PD-0332991 Following Single Dose: Part 1 Phase 1</title>
        <description>AUClast is area under the plasma concentration-time curve from 0 to time of last measurable concentration which is calculated by log-linear trapezoidal method.</description>
        <time_frame>Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-Time Curve From 0 to Time of Last Measurable Concentration (AUClast) of PD-0332991 Following Single Dose: Part 1 Phase 1</title>
          <description>AUClast is area under the plasma concentration-time curve from 0 to time of last measurable concentration which is calculated by log-linear trapezoidal method.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>ng*hr/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="971.7" spread="31"/>
                    <measurement group_id="O2" value="2396" spread="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUClast Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1</title>
        <description>AUClast Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to time of last measurable concentration dose normalized to 125 mg which is calculated by log-linear trapezoidal method.</description>
        <time_frame>Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>AUClast Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1</title>
          <description>AUClast Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to time of last measurable concentration dose normalized to 125 mg which is calculated by log-linear trapezoidal method.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>ng*hr/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1215" spread="31"/>
                    <measurement group_id="O2" value="2396" spread="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Oral Clearance of PD-0332991: Part 1 Phase 1</title>
        <description>Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by AUCinf. AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.</description>
        <time_frame>Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Oral Clearance of PD-0332991: Part 1 Phase 1</title>
          <description>Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by AUCinf. AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>liter per hour (L/hr)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Single dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.43" spread="32"/>
                    <measurement group_id="O2" value="50.29" spread="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Multiple dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="78.43" spread="45"/>
                    <measurement group_id="O2" value="44.03" spread="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Plasma Concentration (Cmax) Of PD-0332991: Part 1 Phase 1</title>
        <description>Cmax is maximum plasma concentration which is observed directly from the actual time-concentration data.</description>
        <time_frame>Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Plasma Concentration (Cmax) Of PD-0332991: Part 1 Phase 1</title>
          <description>Cmax is maximum plasma concentration which is observed directly from the actual time-concentration data.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>nanogram per milliliter (ng/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Single dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.37" spread="15"/>
                    <measurement group_id="O2" value="104.1" spread="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Multiple dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.36" spread="33"/>
                    <measurement group_id="O2" value="185.5" spread="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmax Dose Normalized to 125 mg of PD-0332991: Part 1 Phase 1</title>
        <description>Cmax Dose Normalized to 125 mg is maximum plasma concentration dose normalized to 125 mg which is observed directly from the actual time-concentration data.</description>
        <time_frame>Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax Dose Normalized to 125 mg of PD-0332991: Part 1 Phase 1</title>
          <description>Cmax Dose Normalized to 125 mg is maximum plasma concentration dose normalized to 125 mg which is observed directly from the actual time-concentration data.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Single dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.74" spread="15"/>
                    <measurement group_id="O2" value="104.1" spread="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Multiple dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.72" spread="33"/>
                    <measurement group_id="O2" value="185.5" spread="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pre-dose Plasma Concentration (Ctrough) of PD-0332991 Following Multiple Dose: Part 1 Phase 1</title>
        <description>Ctrough is pre-dose concentration during multiple dosing which is observed directly from the actual time-concentration data.</description>
        <time_frame>Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Pre-dose Plasma Concentration (Ctrough) of PD-0332991 Following Multiple Dose: Part 1 Phase 1</title>
          <description>Ctrough is pre-dose concentration during multiple dosing which is observed directly from the actual time-concentration data.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.51" spread="59"/>
                    <measurement group_id="O2" value="72.76" spread="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Accumulation Ratio (Rac) of PD-0332991 Following Multiple Dose: Part 1 Phase 1</title>
        <description>Rac is the ratio of AUCtau (after multiple doses) to AUCtau (after single dose). AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.</description>
        <time_frame>Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Accumulation Ratio (Rac) of PD-0332991 Following Multiple Dose: Part 1 Phase 1</title>
          <description>Rac is the ratio of AUCtau (after multiple doses) to AUCtau (after single dose). AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>ratio</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.060" lower_limit="1.81" upper_limit="3.54"/>
                    <measurement group_id="O2" value="1.855" lower_limit="1.74" upper_limit="3.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Linearity (Rss) of PD-0332991 Following Multiple Dose: Part 1 Phase 1</title>
        <description>Rss is the ratio of AUCtau (after multiple doses) to AUCinf (after single dose). AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method. AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.</description>
        <time_frame>Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Linearity (Rss) of PD-0332991 Following Multiple Dose: Part 1 Phase 1</title>
          <description>Rss is the ratio of AUCtau (after multiple doses) to AUCinf (after single dose). AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method. AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>ratio</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.130" lower_limit="1.03" upper_limit="1.73"/>
                    <measurement group_id="O2" value="1.105" lower_limit="0.851" upper_limit="1.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991: Part 1 Phase 1</title>
        <description>Tmax is time at which maximum plasma concentration (Cmax) was observed. It was observed directly from data as time of first occurrence.</description>
        <time_frame>Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991: Part 1 Phase 1</title>
          <description>Tmax is time at which maximum plasma concentration (Cmax) was observed. It was observed directly from data as time of first occurrence.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>hour</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Single dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.02" lower_limit="3.97" upper_limit="8.02"/>
                    <measurement group_id="O2" value="4.00" lower_limit="3.90" upper_limit="8.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Multiple dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.02" lower_limit="3.97" upper_limit="6.00"/>
                    <measurement group_id="O2" value="4.02" lower_limit="3.95" upper_limit="6.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Half-Life (t1/2) of PD-0332991: Part 1 Phase 1</title>
        <description>t1/2 is terminal elimination half-life which is calculated by loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.</description>
        <time_frame>Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Half-Life (t1/2) of PD-0332991: Part 1 Phase 1</title>
          <description>t1/2 is terminal elimination half-life which is calculated by loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>hour</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Single dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.72" spread="5.2632"/>
                    <measurement group_id="O2" value="23.93" spread="2.6882"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Multiple dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.75" spread="6.7778"/>
                    <measurement group_id="O2" value="23.15" spread="7.7045"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Volume of Distribution (Vz/F) of PD-0332991 Following Single Dose: Part 1 Phase 1</title>
        <description>Vz/F is apparent volume of distribution estimated from terminal phase, which is calculated as CL/F/kel. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method (AUCinf). kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.</description>
        <time_frame>Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Volume of Distribution (Vz/F) of PD-0332991 Following Single Dose: Part 1 Phase 1</title>
          <description>Vz/F is apparent volume of distribution estimated from terminal phase, which is calculated as CL/F/kel. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method (AUCinf). kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>liter</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3514" spread="25"/>
                    <measurement group_id="O2" value="1730" spread="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration Time Curve Over Dosing Interval (AUCtau) of PD-0332991: Phase 2</title>
        <description>AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.</description>
        <time_frame>0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
            <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration Time Curve Over Dosing Interval (AUCtau) of PD-0332991: Phase 2</title>
          <description>AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>ng*hr/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1979" spread="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Oral Clearance of PD-0332991: Phase 2</title>
        <description>Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by AUCtau. AUCtau is the area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.</description>
        <time_frame>0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
            <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Oral Clearance of PD-0332991: Phase 2</title>
          <description>Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by AUCtau. AUCtau is the area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>L/hr</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63.21" spread="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Plasma Concentration (Cmax) Of PD-0332991: Phase 2</title>
        <description>Cmax is maximum plasma concentration which is observed directly from the actual time-concentration data.</description>
        <time_frame>0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
            <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Plasma Concentration (Cmax) Of PD-0332991: Phase 2</title>
          <description>Cmax is maximum plasma concentration which is observed directly from the actual time-concentration data.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="124.7" spread="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991: Phase 2</title>
        <description>Tmax is time at which maximum plasma concentration (Cmax) was observed. It was observed directly from data as time of first occurrence.</description>
        <time_frame>0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
            <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991: Phase 2</title>
          <description>Tmax is time at which maximum plasma concentration (Cmax) was observed. It was observed directly from data as time of first occurrence.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>hour</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.90" lower_limit="2.00" upper_limit="8.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pre-dose Plasma Concentration (Ctrough) of PD-0332991: Phase 2</title>
        <description>Ctrough is pre-dose concentration during multiple dosing which is observed directly from the actual time-concentration data.</description>
        <time_frame>0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15</time_frame>
        <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
            <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Pre-dose Plasma Concentration (Ctrough) of PD-0332991: Phase 2</title>
          <description>Ctrough is pre-dose concentration during multiple dosing which is observed directly from the actual time-concentration data.</description>
          <population>PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.75" spread="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Objective Response: Phase 1</title>
        <description>Objective response (OR) was defined as a complete response (CR) or partial response (PR) according to the RECIST version 1.1 recorded from first dose of study treatment until disease progression or death due to any cause. CR was defined as disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis &lt;10 millimeter [mm]). PR was defined as a &gt;=30 percent decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Percentage of participants with objective response (who achieved CR or PR) were reported.</description>
        <time_frame>From initiation of treatment up to disease progression (up to 30 months)</time_frame>
        <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O2">
            <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
            <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
          <group group_id="O3">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort</title>
            <description>In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Objective Response: Phase 1</title>
          <description>Objective response (OR) was defined as a complete response (CR) or partial response (PR) according to the RECIST version 1.1 recorded from first dose of study treatment until disease progression or death due to any cause. CR was defined as disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis &lt;10 millimeter [mm]). PR was defined as a &gt;=30 percent decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Percentage of participants with objective response (who achieved CR or PR) were reported.</description>
          <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>With Complete Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>With Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="33.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Objective Response: Phase 2</title>
        <description>Objective response was defined as a complete response (CR) or partial response (PR) according to the RECIST version 1.1 recorded from first dose of study treatment until disease progression or death due to any cause. PD was defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. CR was defined as disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis &lt;10 mm). PR was defined as a &gt;=30% decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Percentage of participants with objective response (who achieved CR or PR) were reported.</description>
        <time_frame>From initiation of treatment up to disease progression (up to 1526 days)</time_frame>
        <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
            <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Objective Response: Phase 2</title>
          <description>Objective response was defined as a complete response (CR) or partial response (PR) according to the RECIST version 1.1 recorded from first dose of study treatment until disease progression or death due to any cause. PD was defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. CR was defined as disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis &lt;10 mm). PR was defined as a &gt;=30% decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Percentage of participants with objective response (who achieved CR or PR) were reported.</description>
          <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DOR): Part 2 Phase 1</title>
        <description>Duration of response was defined as the interval from the first documentation of objective tumor response in participants with CR (disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis &lt;10 millimeter [mm]) or PR (a &gt;=30 percent decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions) according to RECIST version 1.1 to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first.</description>
        <time_frame>baseline up to 1673 days</time_frame>
        <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991). Data for this outcome measure was not summarized and individual participant's data was reported. Here, number of participants analyzed (N) signifies the participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort</title>
            <description>In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DOR): Part 2 Phase 1</title>
          <description>Duration of response was defined as the interval from the first documentation of objective tumor response in participants with CR (disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis &lt;10 millimeter [mm]) or PR (a &gt;=30 percent decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions) according to RECIST version 1.1 to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first.</description>
          <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991). Data for this outcome measure was not summarized and individual participant's data was reported. Here, number of participants analyzed (N) signifies the participants evaluable for this outcome measure.</population>
          <units>days</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participant 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1509"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participant 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1428"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DOR): Phase 2</title>
        <description>Duration of response was defined as the interval from the first documentation of objective tumor response in participants with CR (disappearance of all target lesions with the exception of nodal disease, all target nodes reduced to normal size (short axis &lt;10 mm) or PR (a &gt;=30 % decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions) according to RECIST version 1.1 to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. PD was defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
        <time_frame>From initiation of treatment up to disease progression (up to 1526 days)</time_frame>
        <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991). Here, &quot;Overall Number of Participants Analyzed&quot; (N) signifies the participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
            <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DOR): Phase 2</title>
          <description>Duration of response was defined as the interval from the first documentation of objective tumor response in participants with CR (disappearance of all target lesions with the exception of nodal disease, all target nodes reduced to normal size (short axis &lt;10 mm) or PR (a &gt;=30 % decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions) according to RECIST version 1.1 to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. PD was defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
          <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991). Here, &quot;Overall Number of Participants Analyzed&quot; (N) signifies the participants evaluable for this outcome measure.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.4" lower_limit="19.0" upper_limit="NA">Due to low number of participants with disease progression, upper limit of 95% confidence interval (CI) was not reached.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS): Part 2 Phase 1</title>
        <description>PFS was defined as the time from first dose of study treatment to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PD was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
        <time_frame>baseline up to 1673 days</time_frame>
        <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991). Data for this outcome measure was not summarized and individual participant's data was reported.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort</title>
            <description>In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS): Part 2 Phase 1</title>
          <description>PFS was defined as the time from first dose of study treatment to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PD was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.</description>
          <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991). Data for this outcome measure was not summarized and individual participant's data was reported.</population>
          <units>days</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participant 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1590"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participant 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1593"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participant 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1602"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participant 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participant 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participant 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1512"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Disease Control (DC): Phase 2</title>
        <description>DC: CR, PR or stable disease (SD) for &gt;=24 weeks according to RECIST version (v)1.1 recorded in time period between first dose of study treatment and disease progression or death to any cause. CR: disappearance of all target lesions with exception of nodal disease. All target nodes reduced to normal size (short axis &lt;10 mm). PR: &gt;=30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions. SD was defined as not achieving an OR with confirmed CR or PR according to RECIST v1.1, as determined by investigators, relative to response evaluable population, but remained stable for at least 24 weeks after first dose, then best overall response for such a participant was considered as stable disease. PD was defined using RECIST v1.1 as a 20% increase in sum of longest diameter of target lesions, or a measurable increase in a non-target lesion, or appearance of new lesions.</description>
        <time_frame>From initiation of treatment up to disease progression (up to 1526 days)</time_frame>
        <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
            <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Disease Control (DC): Phase 2</title>
          <description>DC: CR, PR or stable disease (SD) for &gt;=24 weeks according to RECIST version (v)1.1 recorded in time period between first dose of study treatment and disease progression or death to any cause. CR: disappearance of all target lesions with exception of nodal disease. All target nodes reduced to normal size (short axis &lt;10 mm). PR: &gt;=30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions. SD was defined as not achieving an OR with confirmed CR or PR according to RECIST v1.1, as determined by investigators, relative to response evaluable population, but remained stable for at least 24 weeks after first dose, then best overall response for such a participant was considered as stable disease. PD was defined using RECIST v1.1 as a 20% increase in sum of longest diameter of target lesions, or a measurable increase in a non-target lesion, or appearance of new lesions.</description>
          <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS): Phase 2</title>
        <description>Overall survival was defined as the time from first dose of study treatment to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. OS was estimated with Kaplan-Meier method.</description>
        <time_frame>From initiation of treatment up to follow-up period (up to 1526 days)</time_frame>
        <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
            <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS): Phase 2</title>
          <description>Overall survival was defined as the time from first dose of study treatment to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. OS was estimated with Kaplan-Meier method.</description>
          <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="47.5" upper_limit="NA">Due to low number of participants with event, median and upper limit of 95% CI was not reached.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment</title>
        <description>The functional assessment of cancer therapy (FACT) is a modular approach to assess participant's health-related quality of life. FACT-B total score was derived from the sum of these 5 sub-scale scores: physical well-being, social/family well-being and functional well-being (all 3 sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life), emotional well-being (consists of 6 items and ranging from 0 to 24, where higher scores indicating better quality of life, and a breast cancer subscale (consists of 9 items and ranging from 0 to 36, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. FACT-B total score range was of 0 (not at all good) to 144 (very well), where higher scores indicating better quality of life.</description>
        <time_frame>Baseline (Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, End of treatment (up to 1526 days)</time_frame>
        <population>Patient reported outcome (PRO) analysis set included all enrolled participants who receive at least 1 dose of study drug with both baseline and at least 1 complete post-baseline PRO assessment. &quot;Number analyzed&quot; signifies number of participants evaluable for specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
            <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment</title>
          <description>The functional assessment of cancer therapy (FACT) is a modular approach to assess participant's health-related quality of life. FACT-B total score was derived from the sum of these 5 sub-scale scores: physical well-being, social/family well-being and functional well-being (all 3 sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life), emotional well-being (consists of 6 items and ranging from 0 to 24, where higher scores indicating better quality of life, and a breast cancer subscale (consists of 9 items and ranging from 0 to 36, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. FACT-B total score range was of 0 (not at all good) to 144 (very well), where higher scores indicating better quality of life.</description>
          <population>Patient reported outcome (PRO) analysis set included all enrolled participants who receive at least 1 dose of study drug with both baseline and at least 1 complete post-baseline PRO assessment. &quot;Number analyzed&quot; signifies number of participants evaluable for specified time points.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="106.46" lower_limit="101.87" upper_limit="111.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 2: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.20" lower_limit="-4.56" upper_limit="2.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 3: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.22" lower_limit="-6.27" upper_limit="1.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 5: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.38" lower_limit="-6.07" upper_limit="1.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 7: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="35"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.62" lower_limit="-8.43" upper_limit="-0.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 9: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="35"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.45" lower_limit="-7.86" upper_limit="-1.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 11: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.48" lower_limit="-7.99" upper_limit="-0.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 13: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.32" lower_limit="-10.56" upper_limit="-2.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 15: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.06" lower_limit="-7.84" upper_limit="-0.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 17: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.07" lower_limit="-9.48" upper_limit="-2.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 19: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.39" lower_limit="-12.06" upper_limit="-2.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 21: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.85" lower_limit="-10.29" upper_limit="-1.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 23: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.89" lower_limit="-10.97" upper_limit="-0.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 25: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.22" lower_limit="-8.61" upper_limit="0.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 27: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.76" lower_limit="-9.22" upper_limit="-0.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 29: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.26" lower_limit="-10.94" upper_limit="-1.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 31: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.13" lower_limit="-9.46" upper_limit="-0.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 33: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.12" lower_limit="-11.14" upper_limit="-3.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 35: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.68" lower_limit="-11.66" upper_limit="-3.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 37: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.07" lower_limit="-12.56" upper_limit="-3.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 39: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.87" lower_limit="-10.89" upper_limit="-2.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 41: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.70" lower_limit="-11.41" upper_limit="0.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 43: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.42" lower_limit="-17.24" upper_limit="-3.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 45: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.94" lower_limit="-26.09" upper_limit="10.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 47: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.56" lower_limit="-22.48" upper_limit="5.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 49: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.58" lower_limit="-66.70" upper_limit="45.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.17" lower_limit="-13.82" upper_limit="-4.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment</title>
        <description>FACT is a modular approach to assess participant's health-related quality of life. FACT-G total score was derived from the sum of these 4 sub-scale scores: physical well-being, social/family well-being and functional well-being (all 3 sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life), emotional well-being (consists of 6 items and ranging from 0 to 24, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. FACT-G total score range was of 0 (not at all good) to 108 (very well), where higher scores indicating better quality of life.</description>
        <time_frame>Baseline (Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, End of treatment (up to 1526 days)</time_frame>
        <population>Patient reported outcome (PRO) analysis set included all enrolled participants who receive at least 1 dose of study drug with both baseline and at least 1 complete post-baseline PRO assessment. &quot;Number analyzed&quot; signifies number of participants evaluable for specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
            <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment</title>
          <description>FACT is a modular approach to assess participant's health-related quality of life. FACT-G total score was derived from the sum of these 4 sub-scale scores: physical well-being, social/family well-being and functional well-being (all 3 sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life), emotional well-being (consists of 6 items and ranging from 0 to 24, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. FACT-G total score range was of 0 (not at all good) to 108 (very well), where higher scores indicating better quality of life.</description>
          <population>Patient reported outcome (PRO) analysis set included all enrolled participants who receive at least 1 dose of study drug with both baseline and at least 1 complete post-baseline PRO assessment. &quot;Number analyzed&quot; signifies number of participants evaluable for specified time points.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.22" lower_limit="76.21" upper_limit="84.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 2: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.15" lower_limit="-4.10" upper_limit="1.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 3: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.34" lower_limit="-4.72" upper_limit="2.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 5: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.36" lower_limit="-3.21" upper_limit="2.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 7: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="35"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.56" lower_limit="-6.52" upper_limit="-0.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 9: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="35"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.39" lower_limit="-4.94" upper_limit="0.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 11: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.94" lower_limit="-6.79" upper_limit="-1.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 13: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.74" lower_limit="-8.11" upper_limit="-1.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 15: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.98" lower_limit="-6.23" upper_limit="0.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 17: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.64" lower_limit="-7.37" upper_limit="-1.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 19: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.48" lower_limit="-8.94" upper_limit="-2.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 21: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.34" lower_limit="-7.94" upper_limit="-0.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 23: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.39" lower_limit="-8.42" upper_limit="-0.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 25: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.22" lower_limit="-6.94" upper_limit="0.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 27: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.80" lower_limit="-7.34" upper_limit="-0.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 29: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.52" lower_limit="-8.58" upper_limit="-0.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 31: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.55" lower_limit="-8.27" upper_limit="-0.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 33: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.67" lower_limit="-10.26" upper_limit="-3.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 35: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.63" lower_limit="-10.38" upper_limit="-2.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 37: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.49" lower_limit="-10.52" upper_limit="-2.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 39: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.07" lower_limit="-8.37" upper_limit="-1.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 41: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.06" lower_limit="-9.92" upper_limit="-0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 43: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.08" lower_limit="-14.53" upper_limit="0.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 45: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.94" lower_limit="-27.36" upper_limit="15.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 47: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.22" lower_limit="-25.11" upper_limit="12.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 49: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.58" lower_limit="-90.11" upper_limit="72.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.09" lower_limit="-10.98" upper_limit="-3.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Trial Outcome Index (TOI): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment</title>
        <description>FACT is a modular approach to assess participant's health-related quality of life. TOI total score was derived from the sum of the 3 sub-scale scores: physical well-being, functional well-being (both sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life) and breast cancer subscale (consists of 9 items and ranging from 0 to 36, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. TOI total score range was of 0 (not at all good) to 92 (very well), where higher scores indicating better quality of life.</description>
        <time_frame>Baseline (Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, End of treatment (up to 1526 days)</time_frame>
        <population>Patient reported outcome (PRO) analysis set included all enrolled participants who receive at least 1 dose of study drug with both baseline and at least 1 complete post-baseline PRO assessment. &quot;Number analyzed&quot; signifies number of participants evaluable for specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
            <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Trial Outcome Index (TOI): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment</title>
          <description>FACT is a modular approach to assess participant's health-related quality of life. TOI total score was derived from the sum of the 3 sub-scale scores: physical well-being, functional well-being (both sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life) and breast cancer subscale (consists of 9 items and ranging from 0 to 36, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. TOI total score range was of 0 (not at all good) to 92 (very well), where higher scores indicating better quality of life.</description>
          <population>Patient reported outcome (PRO) analysis set included all enrolled participants who receive at least 1 dose of study drug with both baseline and at least 1 complete post-baseline PRO assessment. &quot;Number analyzed&quot; signifies number of participants evaluable for specified time points.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.52" lower_limit="68.36" upper_limit="74.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 2: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="42"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.17" lower_limit="-3.24" upper_limit="0.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 3: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.20" lower_limit="-4.74" upper_limit="0.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 5: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.54" lower_limit="-5.25" upper_limit="0.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 7: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="35"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.63" lower_limit="-6.44" upper_limit="-0.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 9: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="35"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.31" lower_limit="-6.03" upper_limit="-0.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 11: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="33"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.30" lower_limit="-5.06" upper_limit="0.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 13: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.93" lower_limit="-7.31" upper_limit="-0.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 15: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.49" lower_limit="-5.09" upper_limit="0.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 17: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.18" lower_limit="-6.02" upper_limit="-0.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 19: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.32" lower_limit="-8.01" upper_limit="-0.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 21: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.56" lower_limit="-6.83" upper_limit="-0.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 23: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.19" lower_limit="-7.11" upper_limit="0.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 25: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.13" lower_limit="-5.51" upper_limit="1.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 27: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.50" lower_limit="-5.77" upper_limit="0.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 29: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.70" lower_limit="-7.36" upper_limit="-0.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 31: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.95" lower_limit="-5.23" upper_limit="1.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 33: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.30" lower_limit="-7.65" upper_limit="-0.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 35: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.65" lower_limit="-8.68" upper_limit="-0.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 37: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.84" lower_limit="-8.77" upper_limit="-0.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 39: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.47" lower_limit="-7.09" upper_limit="0.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 41: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.27" lower_limit="-7.62" upper_limit="3.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 43: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.00" lower_limit="-13.83" upper_limit="-0.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 45: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.00" lower_limit="-22.40" upper_limit="16.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 47: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.00" lower_limit="-12.96" upper_limit="4.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Cycle 49: Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.00" lower_limit="-14.71" upper_limit="10.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.03" lower_limit="-9.61" upper_limit="-2.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Presence of Tumor Tissue Biomarker- Ki67: Phase 2</title>
        <description>Tumor tissue biomarker, Ki67 was analyzed to investigate possible associations with resistance or sensitivity to treatment with study drugs and was selected based on its known relevance to mechanisms involved in cell cycle regulation. Number of participants with less than or equal to and greater than 20 percent of Ki67 tumor tissue biomarker were reported.</description>
        <time_frame>Baseline (Day 1)</time_frame>
        <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
            <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Presence of Tumor Tissue Biomarker- Ki67: Phase 2</title>
          <description>Tumor tissue biomarker, Ki67 was analyzed to investigate possible associations with resistance or sensitivity to treatment with study drugs and was selected based on its known relevance to mechanisms involved in cell cycle regulation. Number of participants with less than or equal to and greater than 20 percent of Ki67 tumor tissue biomarker were reported.</description>
          <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>&lt;=20 percent</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;20 percent</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Presence of Tumor Tissue Biomarkers- Estrogen Receptor (ER) H-Score, Retinoblastoma (Rb) H-Score, B-cell Lymphoma-1 (BCL-1) H-Score, P16 H-Score: Phase 2</title>
        <description>Tumor tissue biomarkers ER, Rb, BCL-1 and P16 were analyzed to investigate possible associations with resistance or sensitivity to treatment with study drugs and were selected based on their known relevance to mechanisms involved in cell cycle regulation. Number of participants with positive ER (H-Score), Rb (H-Score), BCL-1 (H-Score) and P16 (H-Score) tumor tissue biomarkers were reported. The H-score is a method of assessing the extent of nuclear immunoreactivity, applicable to steroid receptors.</description>
        <time_frame>Baseline (Day 1)</time_frame>
        <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
        <group_list>
          <group group_id="O1">
            <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
            <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Presence of Tumor Tissue Biomarkers- Estrogen Receptor (ER) H-Score, Retinoblastoma (Rb) H-Score, B-cell Lymphoma-1 (BCL-1) H-Score, P16 H-Score: Phase 2</title>
          <description>Tumor tissue biomarkers ER, Rb, BCL-1 and P16 were analyzed to investigate possible associations with resistance or sensitivity to treatment with study drugs and were selected based on their known relevance to mechanisms involved in cell cycle regulation. Number of participants with positive ER (H-Score), Rb (H-Score), BCL-1 (H-Score) and P16 (H-Score) tumor tissue biomarkers were reported. The H-score is a method of assessing the extent of nuclear immunoreactivity, applicable to steroid receptors.</description>
          <population>Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ER (H-Score)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rb (H-Score)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BCL-1 (H-Score)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>P16 (H-Score)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Part 1 Phase 1: Lead-in period (Day -7) up to 28 days after last dose of study drug (up to 308 days), Part 2 Phase 1: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1673 days), Phase 2: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1526 days)</time_frame>
      <desc>Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non serious in another participant, or 1 participant may have experienced both a serious and non serious event during the study. Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).</desc>
      <group_list>
        <group group_id="E1">
          <title>PD-0332991 100 mg: Dose Escalation Cohort</title>
          <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
        </group>
        <group group_id="E2">
          <title>PD-0332991 125 mg: Dose Escalation Cohort</title>
          <description>In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
        </group>
        <group group_id="E3">
          <title>PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort</title>
          <description>In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
        </group>
        <group group_id="E4">
          <title>PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort</title>
          <description>In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal perforation</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Malaise</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral Haemorrhage</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Subarachnoid Haemorrhage</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="42" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Mitral valve incompetence</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctival haemorrhage</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Macular oedema</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="12" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="32" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Cheilitis</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Food poisoning</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Glossitis</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Anal haemorrhage</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Malaise</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Seasonal allergy</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="19" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Angular cheilitis</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Femur fracture</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="12" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="11" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="34" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="30" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hypermagnesaemia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal stiffness</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Osteoporosis</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Cancer pain</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Tumour pain</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Parosmia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Sensory disturbance</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Dysaesthesia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety disorder</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Calculus urinary</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Genital haemorrhage</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Asthma</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Rhinitis allergic</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract inflammation</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Upper-airway cough syndrome</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Nail disorder</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Dermal cyst</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Haemorrhage subcutaneous</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysaesthesia syndrome</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Hot Flush</sub_title>
                <description>MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Pfizer ClinicalTrials.gov Call Center</name_or_title>
      <organization>Pfizer Inc.</organization>
      <phone>1-800-718-1021</phone>
      <email>ClinicalTrials.gov_Inquiries@pfizer.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01684215
org study id: A5481010
nct id: NCT01684215
lead sponsor: 
has dmc: No
This study is comprised of two portions: a Phase 1 portion and a Phase 2 portion. The Phase 1
      portion is a single-country, non-randomized, open label, clinical trial which will evaluate
      the safety, tolerability, preliminary efficacy, and PK profile of PD-0332991 as a single
      agent in Japanese patients with advanced solid tumors, and PD-0332991 in combination with
      letrozole in the first-line treatment of Japanese patients with ER(+) HER2(-) ABC. The Phase
      2 portion is a single-country, non-randomized, open-label, single-cohort, multi-center
      clinical trial to evaluate the efficacy and safety of PD-0332991 in combination with
      letrozole for the first-line treatment of postmenopausal Japanese patients with ER(+) HER2(-)
      ABC.
allocation: Non-Randomized
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Dose Limiting Toxicities (DLT): Part 1 Phase 1
time frame: Lead-in period (Day -7) up to Day 28 (Cycle 1)
description: DLT was classified as per common terminology criteria for adverse events (CTCAE) version 4.0 as any of the events occurring during 28 days of Cycle 1,attributed to study drug:grade 4 neutropenia(for a duration of greater than [>]7 days); febrile neutropenia (grade greater than or equal to [>=]3 neutropenia,body temperature >=38.5 degree Celsius);grade >=3 thrombocytopenia with bleeding episode;grade 4 thrombocytopenia;grade >=3 non-hematologic toxicity except grade 3 or more nausea, vomiting,electrolyte abnormality(if controllable by therapy);grade 3 QTc prolongation(>500 millisecond [msec])persist after correction of reversible cause such as electrolyte abnormalities or hypoxia. Lack of hematologic recovery (platelets less than [<]50,000/microliter [mcL],absolute neutrophil count <1,000/mcL,hemoglobin <8.0 gram/deciliter [g/dL]) or prolonged non hematologic toxicities that delays initiation of next dose by >7 days;receipt of <75 percent of planned dose in first cycle due to toxicity.
measure: Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2 Phase 1
time frame: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1673 days)
description: A treatment related AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Relatedness was judged by investigator. AEs included both serious and non-serious adverse events.
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) By Severity: Part 2 Phase 1
time frame: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1673 days)
description: AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment but increased in National Cancer Institute (NCI) CTCAE grade during study treatment period. AE severity was defined to be the maximum toxicity grade of the TEAEs experienced by the participants during the study. AE was assessed according to severity as: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE).
measure: Percentage of Participants With 1 Year Progression Free Survival (PFS): Phase 2
time frame: From initiation of treatment up to 12 months
description: PFS was defined as the time from first dose of study treatment to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD, whichever occurred first. PD was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.1-year PFS was defined as the percentage of participants without PFS events (PD or death due to any cause) at 12 months based on the Kaplan-Meier estimate. Percentage of participants with 1-year PFS with 90% confidence interval (CI) were reported.
measure: Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Phase 1 (Part 1) and Phase 2
time frame: Part 1 Phase 1: Lead-in period (Day -7) up to 28 days after last dose of study drug (up to 308 days), Phase 2: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1526 days)
description: A treatment related AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Relatedness was judged by investigator. AEs included both serious and non-serious adverse events.
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) By Severity: Phase 1 (Part 1) and Phase 2
time frame: Part 1 Phase 1: Lead-in period (Day -7) up to 28 days after last dose of study drug (up to 308 days), Phase 2: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1526 days)
description: AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment but increased in NCI CTCAE version 4.0 grade during study treatment period. AE severity was defined to be the maximum toxicity grade of the TEAEs experienced by the participants during the study. AE was assessed according to severity as: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE).
measure: Number of Participants With Clinically Significant Laboratory Abnormalities
time frame: Part 1 Phase 1: Lead-in period (Day -7) up to 308 days; Part 2 Phase 1: Baseline (Day 1) up to 1673 days; Phase 2: Baseline (Day 1) up to 1526 days
description: Abnormality criteria: hemoglobin: <0.8*lower limit of normal [LLN], platelets: <0.5*LLN or >1.75*upper limit of normal [ULN], leukocytes: <0.6*LLN or >1.5*ULN, lymphocytes, total neutrophils: <0.8*LLN or >1.2*ULN, basophils, eosinophil,monocytes: >1.2*ULN); aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase (GT): >0.3*ULN, total protein, albumin: <0.8*LLN or >1.2*ULN, total bilirubin, direct bilirubin: >1.5*ULN; blood urea nitrogen, creatinine: >1.3*ULN, uric acid: >1.2*ULN; sodium: <0.95*LLN or >1.05*ULN, potassium, chloride, calcium, magnesium: <0.9*LLN or >1.1*ULN, phosphate: <0.8*LLN or >1.2*ULN; creatine kinase: >2.0*ULN, glucose fasting: <0.6*LLN or >1.5*ULN, glycosylated haemoglobin: >1.3*ULN;urinalysis dipstick (urine protein, urine blood >=1); urine protein 24 hour: >1.1*ULN; coagulation Activated partial thromboplastin time [APTT], Prothrombin, prothrombin international ratio: >1.1*ULN.
measure: Area Under the Plasma Concentration Time Curve Over Dosing Interval (AUCtau) of PD-0332991 Following Multiple Dose: Part 1 Phase 1
time frame: Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8
description: AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.
measure: AUCtau Dose Normalized to 125 Milligram (mg) of PD-0332991 Following Multiple Dose: Part 1 Phase 1
time frame: Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8
description: AUCtau Dose Normalized to 125 mg is area under the plasma concentration-time curve over dosing interval dose normalized to 125 mg which is calculated by log-linear trapezoidal method.
measure: Area Under the Plasma Concentration-Time Curve From 0 to Time 24 Hours (AUC24) of PD-0332991 Following Single Dose: Part 1 Phase 1
time frame: Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12 and 24 hours post-dose in Lead-in period (Day -7)
description: AUC24 is area under the plasma concentration-time curve from 0 to time 24 hours which is calculated by log-linear trapezoidal method.
measure: AUC24 Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1
time frame: Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12 and 24 hours post-dose in Lead-in period (Day -7)
description: AUC24 Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to time 24 hours dose normalized to 125 mg which is calculated by log-linear trapezoidal method.
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of PD-0332991 Following Single Dose: Part 1 Phase 1
time frame: Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)
description: AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.
measure: AUCinf Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1
time frame: Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)
description: AUCinf Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to infinity dose normalized to 125 mg which is calculated by log-linear trapezoidal method.
measure: Area Under the Plasma Concentration-Time Curve From 0 to Time of Last Measurable Concentration (AUClast) of PD-0332991 Following Single Dose: Part 1 Phase 1
time frame: Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)
description: AUClast is area under the plasma concentration-time curve from 0 to time of last measurable concentration which is calculated by log-linear trapezoidal method.
measure: AUClast Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1
time frame: Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)
description: AUClast Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to time of last measurable concentration dose normalized to 125 mg which is calculated by log-linear trapezoidal method.
measure: Apparent Oral Clearance of PD-0332991: Part 1 Phase 1
time frame: Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8
description: Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by AUCinf. AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.
measure: Maximum Observed Plasma Concentration (Cmax) Of PD-0332991: Part 1 Phase 1
time frame: Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8
description: Cmax is maximum plasma concentration which is observed directly from the actual time-concentration data.
measure: Cmax Dose Normalized to 125 mg of PD-0332991: Part 1 Phase 1
time frame: Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8
description: Cmax Dose Normalized to 125 mg is maximum plasma concentration dose normalized to 125 mg which is observed directly from the actual time-concentration data.
measure: Pre-dose Plasma Concentration (Ctrough) of PD-0332991 Following Multiple Dose: Part 1 Phase 1
time frame: Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8
description: Ctrough is pre-dose concentration during multiple dosing which is observed directly from the actual time-concentration data.
measure: Accumulation Ratio (Rac) of PD-0332991 Following Multiple Dose: Part 1 Phase 1
time frame: Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8
description: Rac is the ratio of AUCtau (after multiple doses) to AUCtau (after single dose). AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.
measure: Linearity (Rss) of PD-0332991 Following Multiple Dose: Part 1 Phase 1
time frame: Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8
description: Rss is the ratio of AUCtau (after multiple doses) to AUCinf (after single dose). AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method. AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991: Part 1 Phase 1
time frame: Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8
description: Tmax is time at which maximum plasma concentration (Cmax) was observed. It was observed directly from data as time of first occurrence.
measure: Terminal Half-Life (t1/2) of PD-0332991: Part 1 Phase 1
time frame: Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8
description: t1/2 is terminal elimination half-life which is calculated by loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
measure: Volume of Distribution (Vz/F) of PD-0332991 Following Single Dose: Part 1 Phase 1
time frame: Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)
description: Vz/F is apparent volume of distribution estimated from terminal phase, which is calculated as CL/F/kel. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method (AUCinf). kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
measure: Area Under the Plasma Concentration Time Curve Over Dosing Interval (AUCtau) of PD-0332991: Phase 2
time frame: 0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15
description: AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.
measure: Apparent Oral Clearance of PD-0332991: Phase 2
time frame: 0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15
description: Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by AUCtau. AUCtau is the area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.
measure: Maximum Observed Plasma Concentration (Cmax) Of PD-0332991: Phase 2
time frame: 0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15
description: Cmax is maximum plasma concentration which is observed directly from the actual time-concentration data.
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991: Phase 2
time frame: 0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15
description: Tmax is time at which maximum plasma concentration (Cmax) was observed. It was observed directly from data as time of first occurrence.
measure: Pre-dose Plasma Concentration (Ctrough) of PD-0332991: Phase 2
time frame: 0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15
description: Ctrough is pre-dose concentration during multiple dosing which is observed directly from the actual time-concentration data.
measure: Percentage of Participants With Objective Response: Phase 1
time frame: From initiation of treatment up to disease progression (up to 30 months)
description: Objective response (OR) was defined as a complete response (CR) or partial response (PR) according to the RECIST version 1.1 recorded from first dose of study treatment until disease progression or death due to any cause. CR was defined as disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis <10 millimeter [mm]). PR was defined as a >=30 percent decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Percentage of participants with objective response (who achieved CR or PR) were reported.
measure: Percentage of Participants With Objective Response: Phase 2
time frame: From initiation of treatment up to disease progression (up to 1526 days)
description: Objective response was defined as a complete response (CR) or partial response (PR) according to the RECIST version 1.1 recorded from first dose of study treatment until disease progression or death due to any cause. PD was defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. CR was defined as disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis <10 mm). PR was defined as a >=30% decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Percentage of participants with objective response (who achieved CR or PR) were reported.
measure: Duration of Response (DOR): Part 2 Phase 1
time frame: baseline up to 1673 days
description: Duration of response was defined as the interval from the first documentation of objective tumor response in participants with CR (disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis <10 millimeter [mm]) or PR (a >=30 percent decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions) according to RECIST version 1.1 to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first.
measure: Duration of Response (DOR): Phase 2
time frame: From initiation of treatment up to disease progression (up to 1526 days)
description: Duration of response was defined as the interval from the first documentation of objective tumor response in participants with CR (disappearance of all target lesions with the exception of nodal disease, all target nodes reduced to normal size (short axis <10 mm) or PR (a >=30 % decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions) according to RECIST version 1.1 to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. PD was defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
measure: Progression Free Survival (PFS): Part 2 Phase 1
time frame: baseline up to 1673 days
description: PFS was defined as the time from first dose of study treatment to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PD was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
measure: Percentage of Participants With Disease Control (DC): Phase 2
time frame: From initiation of treatment up to disease progression (up to 1526 days)
description: DC: CR, PR or stable disease (SD) for >=24 weeks according to RECIST version (v)1.1 recorded in time period between first dose of study treatment and disease progression or death to any cause. CR: disappearance of all target lesions with exception of nodal disease. All target nodes reduced to normal size (short axis <10 mm). PR: >=30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions. SD was defined as not achieving an OR with confirmed CR or PR according to RECIST v1.1, as determined by investigators, relative to response evaluable population, but remained stable for at least 24 weeks after first dose, then best overall response for such a participant was considered as stable disease. PD was defined using RECIST v1.1 as a 20% increase in sum of longest diameter of target lesions, or a measurable increase in a non-target lesion, or appearance of new lesions.
measure: Overall Survival (OS): Phase 2
time frame: From initiation of treatment up to follow-up period (up to 1526 days)
description: Overall survival was defined as the time from first dose of study treatment to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. OS was estimated with Kaplan-Meier method.
measure: Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment
time frame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, End of treatment (up to 1526 days)
description: The functional assessment of cancer therapy (FACT) is a modular approach to assess participant's health-related quality of life. FACT-B total score was derived from the sum of these 5 sub-scale scores: physical well-being, social/family well-being and functional well-being (all 3 sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life), emotional well-being (consists of 6 items and ranging from 0 to 24, where higher scores indicating better quality of life, and a breast cancer subscale (consists of 9 items and ranging from 0 to 36, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. FACT-B total score range was of 0 (not at all good) to 144 (very well), where higher scores indicating better quality of life.
measure: Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment
time frame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, End of treatment (up to 1526 days)
description: FACT is a modular approach to assess participant's health-related quality of life. FACT-G total score was derived from the sum of these 4 sub-scale scores: physical well-being, social/family well-being and functional well-being (all 3 sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life), emotional well-being (consists of 6 items and ranging from 0 to 24, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. FACT-G total score range was of 0 (not at all good) to 108 (very well), where higher scores indicating better quality of life.
measure: Change From Baseline in Trial Outcome Index (TOI): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment
time frame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, End of treatment (up to 1526 days)
description: FACT is a modular approach to assess participant's health-related quality of life. TOI total score was derived from the sum of the 3 sub-scale scores: physical well-being, functional well-being (both sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life) and breast cancer subscale (consists of 9 items and ranging from 0 to 36, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. TOI total score range was of 0 (not at all good) to 92 (very well), where higher scores indicating better quality of life.
measure: Presence of Tumor Tissue Biomarker- Ki67: Phase 2
time frame: Baseline (Day 1)
description: Tumor tissue biomarker, Ki67 was analyzed to investigate possible associations with resistance or sensitivity to treatment with study drugs and was selected based on its known relevance to mechanisms involved in cell cycle regulation. Number of participants with less than or equal to and greater than 20 percent of Ki67 tumor tissue biomarker were reported.
measure: Presence of Tumor Tissue Biomarkers- Estrogen Receptor (ER) H-Score, Retinoblastoma (Rb) H-Score, B-cell Lymphoma-1 (BCL-1) H-Score, P16 H-Score: Phase 2
time frame: Baseline (Day 1)
description: Tumor tissue biomarkers ER, Rb, BCL-1 and P16 were analyzed to investigate possible associations with resistance or sensitivity to treatment with study drugs and were selected based on their known relevance to mechanisms involved in cell cycle regulation. Number of participants with positive ER (H-Score), Rb (H-Score), BCL-1 (H-Score) and P16 (H-Score) tumor tissue biomarkers were reported. The H-score is a method of assessing the extent of nuclear immunoreactivity, applicable to steroid receptors.
arm group label: Single-agent PD-0332991
arm group type: Experimental
description: Phase 1 Part 1
arm group label: PD-0332991 in combination with letrozole
arm group type: Experimental
description: Phase 1 Part 2
arm group label: PD-0332991 with letrozole
arm group type: Experimental
description: Phase 2
intervention type: Drug
intervention name: PD-0332991
description: PD-0332991 (100 mg or 125 mg) will be orally administered once a day for 3 weeks followed by 1 week off treatment, in the morning on an empty stomach. Dose reduction of PD-0332991 by one (100 mg) or two (75 mg) dose level is permitted depending on treatment related toxicity.
arm group label: Single-agent PD-0332991
intervention type: Drug
intervention name: PD-0332991
description: PD-0332991, 125 mg, will be orally administered with food once a day for 3 weeks followed by 1 week off treatment. PD-0332991 will be administered once a day together with letrozole. Dose reduction of PD-0332991 by one (100 mg) or two (75 mg) dose level is permitted depending on treatment related toxicity.
arm group label: PD-0332991 in combination with letrozole
intervention type: Drug
intervention name: letrozole
description: Letrozole, 2.5 mg, will be orally administered once a day in continuous daily dosing together with PD-0332991. Dose reduction of letrozole is not permitted, but dosing interruptions for letrozole-related toxicity are allowed as per investigator's medical judgement.
arm group label: PD-0332991 in combination with letrozole
intervention type: Drug
intervention name: PD-0332991
description: PD-0332991, 125 mg, will be orally administered with food once a day for 3 weeks followed by 1 week off treatment. PD-0332991 will be administered once a day together with letrozole. Dose reduction of PD-0332991 by one (100 mg) or two (75 mg) dose level is permitted depending on treatment related toxicity.
arm group label: PD-0332991 with letrozole
intervention type: Drug
intervention name: letrozole
description: Letrozole, 2.5 mg, will be orally administered once a day in continuous daily dosing together with PD-0332991. Dose reduction of letrozole is not permitted, but dosing interruptions for letrozole-related toxicity are allowed as per investigator's medical judgement.
arm group label: PD-0332991 with letrozole
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
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country: Japan
url: https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A5481010&StudyName=A%20Study%20Of%20Oral%20Palbociclib%20%28PD-0332991%29%2C%20A%20CDK4/6%20Inhibitor%2C%20As%20Single%20Agent%20In%20Japanese%20Patients%20With%20Advanced%20Solid%20Tumors%20Or
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Neoplasms
mesh term: Letrozole
mesh term: Palbociclib
sharing ipd: Yes
ipd description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
ipd url: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
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