<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/NCT01730833</url>
  </required_header>
  <id_info>
    <org_study_id>12147</org_study_id>
    <secondary_id>NCI-2012-02371</secondary_id>
    <secondary_id>R01CA166020</secondary_id>
    <secondary_id>AACR Grant 12-60-26-WANG</secondary_id>
    <nct_id>NCT01730833</nct_id>
  </id_info>
  <brief_title>Pertuzumab, Trastuzumab, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With HER2-Positive Advanced Breast Cancer</brief_title>
  <official_title>Phase II Prospective Open Label Study of Pertuzumab, Trastuzumab, and Nab-Paclitaxel in Patients With HER-2 Positive Advanced Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>City of Hope Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>City of Hope Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well pertuzumab, trastuzumab, and paclitaxel&#xD;
      albumin-stabilized nanoparticle formulation work in treating patients with human epidermal&#xD;
      growth factor receptor (HER) 2-positive stage II-IV breast cancer. Monoclonal antibodies,&#xD;
      such as pertuzumab and trastuzumab, can block tumor growth in different ways. Some block the&#xD;
      ability of tumor cells to grow and spread. Others find tumor cells and help kill them or&#xD;
      carry tumor-killing substances to them. Drugs used in chemotherapy, such as paclitaxel&#xD;
      albumin-stabilized nanoparticle formulation, work in different ways to kill tumor cells or&#xD;
      stop them from growing. Giving pertuzumab and trastuzumab together with paclitaxel&#xD;
      albumin-stabilized nanoparticle formulation may be a better way to block tumor growth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine efficacy of administration of pertuzumab in combination with trastuzumab with&#xD;
      nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) in subjects with&#xD;
      stage IV human epidermal growth factor receptor (HER)-2 overexpressing metastatic breast&#xD;
      cancer (MBC) as measured by progression free survival (PFS).&#xD;
&#xD;
      II. To determine the efficacy as neoadjuvant treatment of the regimen in HER2+ locally&#xD;
      advanced breast cancer (LABC) as defined by pathologic complete response (pCR).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the safety of pertuzumab when added to trastuzumab and nab-paclitaxel in HER-2&#xD;
      overexpressing MBC and LABC cancer as assessed by the frequency and severity of adverse&#xD;
      events (AEs), abnormal findings on physical examination, laboratory tests, and vital signs.&#xD;
&#xD;
      II. To evaluate the objective response rate (Response Evaluation Criteria in Solid Tumors&#xD;
      [RECIST] 1.1) and duration of response in MBC.&#xD;
&#xD;
      III. To evaluate the efficacy of the regimen by assessing tumor response including assessment&#xD;
      of residual cancer burden (RCB) scores in LABC.&#xD;
&#xD;
      IV. To assess the progression free survival (MBC), relapse-free survival (LABC) and overall&#xD;
      survival in all patients.&#xD;
&#xD;
      V. To perform exploratory circulatory gene, micro-ribonucleic acid (RNA), and exosome&#xD;
      profiling as well as protein and glycomic profiling.&#xD;
&#xD;
      VI. To assess the feasibility of molecular profiling in both primary and metastatic tumor&#xD;
      samples.&#xD;
&#xD;
      VII. To assess numerical and qualitative aspects of circulating tumor cells and circulating&#xD;
      tumor-derived deoxyribonucleic acid (DNA).&#xD;
&#xD;
      OUTLINE: Patients receive pertuzumab intravenously (IV) over 30-60 minutes on day 1,&#xD;
      trastuzumab IV over 30-90 minutes and paclitaxel albumin-stabilized nanoparticle formulation&#xD;
      IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days in the absence of&#xD;
      disease progression or unacceptable toxicity (patients with MBC) or for 6 courses in the&#xD;
      absence of disease progression or unacceptable toxicity (patients with LABC).&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months for 4 years and&#xD;
      then every 6 months for 1 year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 17, 2013</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Actual">January 12, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression Free Survival (MBC Cohort)</measure>
    <time_frame>assessed up to 5 years</time_frame>
    <description>Estimated using the product-limit method of Kaplan and Meier. From time of initial treatment until disease progression or death. Progression is 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>
  </primary_outcome>
  <primary_outcome>
    <measure>Five Year Disease-free Survival (LABC Cohort)</measure>
    <time_frame>assessed up to 5 years</time_frame>
    <description>Estimated using the method of Kaplan-Meier. Disease-free survival is defined as the time from Initial treatment to recurrence of tumor or death</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Response (MBC Cohort)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Five Year Overall Survival</measure>
    <time_frame>Assessed up to 5 years</time_frame>
    <description>Estimated by the Kaplan-Meier method. From the initial date of treatment to date of death from any cause.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">63</enrollment>
  <condition>HER2-positive Breast Cancer</condition>
  <condition>Recurrent Breast Cancer</condition>
  <condition>Stage IIA Breast Cancer</condition>
  <condition>Stage IIB Breast Cancer</condition>
  <condition>Stage IIIA Breast Cancer</condition>
  <condition>Stage IIIB Breast Cancer</condition>
  <condition>Stage IIIC Breast Cancer</condition>
  <condition>Stage IV Breast Cancer</condition>
  <condition>Breast Adenocarcinoma</condition>
  <condition>Inflammatory Breast Carcinoma</condition>
  <arm_group>
    <arm_group_label>Treatment (pertuzumab, trastuzumab, nab-paclitaxel)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive pertuzumab IV over 30-60 minutes on day 1, trastuzumab IV over 30-90 minutes and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>pertuzumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (pertuzumab, trastuzumab, nab-paclitaxel)</arm_group_label>
    <other_name>2C4 antibody</other_name>
    <other_name>monoclonal antibody 2C4</other_name>
    <other_name>Perjeta</other_name>
    <other_name>rhuMAb-2C4</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>trastuzumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (pertuzumab, trastuzumab, nab-paclitaxel)</arm_group_label>
    <other_name>anti-c-erB-2</other_name>
    <other_name>Herceptin</other_name>
    <other_name>MOAB HER2</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>paclitaxel albumin-stabilized nanoparticle formulation</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (pertuzumab, trastuzumab, nab-paclitaxel)</arm_group_label>
    <other_name>ABI-007</other_name>
    <other_name>nab paclitaxel</other_name>
    <other_name>nab-paclitaxel</other_name>
    <other_name>nanoparticle albumin-bound paclitaxel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>laboratory biomarker analysis</intervention_name>
    <description>Optional correlative studies</description>
    <arm_group_label>Treatment (pertuzumab, trastuzumab, nab-paclitaxel)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must be diagnosed with metastatic cytologically or histologically confirmed&#xD;
             adenocarcinoma of the breast with HER2 over-expression or with newly diagnosed locally&#xD;
             advanced (including inflammatory) breast cancer (LABC) with stage II-III disease;&#xD;
             patients with metastatic (stage IV) disease (MBC) must have measurable lesions&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control or abstinence) prior to study entry and&#xD;
             for six months following duration of study participation; should a woman become&#xD;
             pregnant or suspect that she is pregnant while participating on the trial, she should&#xD;
             inform her treating physician immediately&#xD;
&#xD;
          -  Tumor positive or negative for expression of hormone receptors (&lt; 1% or &gt; 1%) and&#xD;
             overexpressing HER2 by immunohistochemistry (IHC) (3+), or, HER2-amplified by&#xD;
             fluorescence in situ hybridization (FISH) or by alternative gene testing&#xD;
&#xD;
          -  For patients with LABC, no prior therapy is allowed&#xD;
&#xD;
          -  For patients with MBC, prior adjuvant chemotherapy and trastuzumab more than or equal&#xD;
             to 12 months prior to enrollment are allowed&#xD;
&#xD;
          -  No prior chemotherapy or trastuzumab for treatment of metastatic breast cancer&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) &gt;= 50% (determined by echocardiogram or&#xD;
             multigated acquisition scan) within 42 days of treatment&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group performance status of 0 or 1&#xD;
&#xD;
          -  Hemoglobin &gt;= 9 g/dl&#xD;
&#xD;
          -  Leukocytes &gt;= 3.0 x 10^9/L&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1.5 x 10^9/L&#xD;
&#xD;
          -  Platelets &gt;= 100 x 10^9/L&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.3 mg/dl (institutional upper limit of normal)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase&#xD;
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])&#xD;
             =&lt; 2 x institutional upper limit of normal&#xD;
&#xD;
          -  Creatinine within normal institutional limits or creatinine clearance &gt; 50 mL/min/1.73&#xD;
             m^2 for patients with creatinine levels above institutional normal (using&#xD;
             Cockcroft-Gault formula)&#xD;
&#xD;
          -  All radiology studies (study requiring staging) must be performed within 35 days prior&#xD;
             to the start of therapy&#xD;
&#xD;
          -  No serious medical conditions such as myocardial infarction within 6 months prior to&#xD;
             entry, congestive heart failure, unstable ventricular arrhythmia, uncontrolled&#xD;
             hypertension, uncontrolled diabetes mellitus, uncontrolled psychotic disorders,&#xD;
             serious infections, active peptic ulcer disease, psychiatric illness, or any other&#xD;
             medical conditions that might be aggravated by treatment or limit compliance&#xD;
&#xD;
          -  Currently, no active second malignancy other than non-melanoma skin cancer; note:&#xD;
             patients are not considered to have a &quot;current active&quot; malignancy if they have&#xD;
             completed anti-cancer therapy and are considered by their physicians to have a less&#xD;
             than 30% chance of relapse&#xD;
&#xD;
          -  All patients must have the ability to understand and the willingness to sign an&#xD;
             informed consent&#xD;
&#xD;
          -  Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test at&#xD;
             screening for patients of child-bearing potential&#xD;
&#xD;
          -  No prior therapies (except for anti-estrogen therapy) are allowed for the treatment of&#xD;
             the newly diagnosed metastatic breast cancer; patients are allowed to have had prior&#xD;
             chemotherapy for breast cancer in the adjuvant setting for at least 12 months prior to&#xD;
             enrollment into this study; patients with a prior diagnosis of malignancy treated &gt;= 5&#xD;
             years ago are eligible, provided that they have not received prior nab-paclitaxel as&#xD;
             part of their prior treatment regimen, and that they meet all eligibility criteria&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known active hepatitis B or C&#xD;
&#xD;
          -  Known active human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Prior breast cancer or other invasive malignancy treated within 5 years&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Neuropathy &gt; grade 1&#xD;
&#xD;
          -  Any other intercurrent medical/psychological problem deemed exclusionary by the&#xD;
             treating physician or investigators/principal investigator (PI)&#xD;
&#xD;
          -  Cumulative dose of doxorubicin or equivalent of &gt; 360 mg/m^2 during prior adjuvant&#xD;
             therapy&#xD;
&#xD;
          -  LVEF &lt; 50% during previous trastuzumab therapy&#xD;
&#xD;
          -  Central nervous system metastases&#xD;
&#xD;
          -  Another malignancy excluding basal cell skin cancer&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Subjects will be excluded who, in the opinion of the investigator, may not be able to&#xD;
             comply with the safety monitoring requirements of the study&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joanne Mortimer, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>City of Hope Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope Antelope Valley</name>
      <address>
        <city>Lancaster</city>
        <state>California</state>
        <zip>93534</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope- South Pasadena Cancer Center</name>
      <address>
        <city>South Pasadena</city>
        <state>California</state>
        <zip>91030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>November 16, 2012</study_first_submitted>
  <study_first_submitted_qc>November 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <results_first_submitted>March 10, 2023</results_first_submitted>
  <results_first_submitted_qc>June 26, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">June 28, 2023</results_first_posted>
  <last_update_submitted>June 26, 2023</last_update_submitted>
  <last_update_submitted_qc>June 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Inflammatory Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Albumin-Bound Paclitaxel</mesh_term>
    <mesh_term>Trastuzumab</mesh_term>
    <mesh_term>Pertuzumab</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 27, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/33/NCT01730833/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Cohort1: Stage IV HER-2 Overexpressing Metastatic Breast Cancer (MBC) Patients</title>
          <description>Pertuzumab administered as 840 mg IV during cycle 1 followed by 420 mg IV once every three weeks starting cycle 2.&#xD;
Trastuzumab loading dose of 4mg/kg IV for week one followed by 2mg/kg IV weekly.&#xD;
Nab-paclitaxel 100 mg/m2 IV weekly.&#xD;
Treatment is scheduled to continue until:&#xD;
Disease progression Unmanageable toxicity Primary physician or patient request to discontinue therapy Study termination by the sponsors</description>
        </group>
        <group group_id="P2">
          <title>Cohort 2: HER2+ Locally Advanced Breast Cancer (LABC) Patients</title>
          <description>Pertuzumab administered as 840 mg IV during cycle 1 followed by 420 mg IV once every three weeks starting cycle 2.&#xD;
Trastuzumab loading dose of 4mg/kg IV for week one followed by 2mg/kg IV weekly.&#xD;
Nab-paclitaxel 100 mg/m2 IV weekly.&#xD;
Treatment is scheduled to continue until:&#xD;
A planned 6 cycles Unmanageable toxicity Primary physician or patient request to discontinue therapy Study termination by the sponsors</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="45"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="45"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cohort1: Stage IV HER-2 Overexpressing Metastatic Breast Cancer (MBC) Patients</title>
          <description>Pertuzumab administered as 840 mg IV during cycle 1 followed by 420 mg IV once every three weeks starting cycle 2.&#xD;
Trastuzumab loading dose of 4mg/kg IV for week one followed by 2mg/kg IV weekly.&#xD;
Nab-paclitaxel 100 mg/m2 IV weekly.&#xD;
Treatment is scheduled to continue until:&#xD;
Disease progression Unmanageable toxicity Primary physician or patient request to discontinue therapy Study termination by the sponsors</description>
        </group>
        <group group_id="B2">
          <title>Cohort 2: HER2+ Locally Advanced Breast Cancer (LABC) Patients</title>
          <description>Pertuzumab administered as 840 mg IV during cycle 1 followed by 420 mg IV once every three weeks starting cycle 2.&#xD;
Trastuzumab loading dose of 4mg/kg IV for week one followed by 2mg/kg IV weekly.&#xD;
Nab-paclitaxel 100 mg/m2 IV weekly.&#xD;
Treatment is scheduled to continue until:&#xD;
A planned 6 cycles Unmanageable toxicity Primary physician or patient request to discontinue therapy Study termination by the sponsors</description>
        </group>
        <group group_id="B3">
          <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="18"/>
            <count group_id="B2" value="45"/>
            <count group_id="B3" value="63"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49" lower_limit="31" upper_limit="65"/>
                    <measurement group_id="B2" value="56" lower_limit="31" upper_limit="78"/>
                    <measurement group_id="B3" value="54" lower_limit="31" upper_limit="78"/>
                  </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="18"/>
                    <measurement group_id="B2" value="45"/>
                    <measurement group_id="B3" value="63"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-Hispanic White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="45"/>
                    <measurement group_id="B3" value="63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Progression Free Survival (MBC Cohort)</title>
        <description>Estimated using the product-limit method of Kaplan and Meier. From time of initial treatment until disease progression or death. Progression is 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>assessed up to 5 years</time_frame>
        <population>PFS was not performed on the LABC cohort (neoadjuvant patients). A more relevant analysis, Disease-free survival is present elsewhere in these results.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort1: Stage IV HER-2 Overexpressing Metastatic Breast Cancer (MBC) Patients</title>
            <description>Pertuzumab administered as 840 mg IV during cycle 1 followed by 420 mg IV once every three weeks starting cycle 2.&#xD;
Trastuzumab loading dose of 4mg/kg IV for week one followed by 2mg/kg IV weekly.&#xD;
Nab-paclitaxel 100 mg/m2 IV weekly.&#xD;
Treatment is scheduled to continue until:&#xD;
Disease progression Unmanageable toxicity Primary physician or patient request to discontinue therapy Study termination by the sponsors</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: HER2+ Locally Advanced Breast Cancer (LABC) Patients</title>
            <description>Pertuzumab administered as 840 mg IV during cycle 1 followed by 420 mg IV once every three weeks starting cycle 2.&#xD;
Trastuzumab loading dose of 4mg/kg IV for week one followed by 2mg/kg IV weekly.&#xD;
Nab-paclitaxel 100 mg/m2 IV weekly.&#xD;
Treatment is scheduled to continue until:&#xD;
A planned 6 cycles Unmanageable toxicity Primary physician or patient request to discontinue therapy Study termination by the sponsors</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (MBC Cohort)</title>
          <description>Estimated using the product-limit method of Kaplan and Meier. From time of initial treatment until disease progression or death. Progression is 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>PFS was not performed on the LABC cohort (neoadjuvant patients). A more relevant analysis, Disease-free survival is present elsewhere in these results.</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="18"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.4" lower_limit="7.1" upper_limit="NA">NA - The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Five Year Disease-free Survival (LABC Cohort)</title>
        <description>Estimated using the method of Kaplan-Meier. Disease-free survival is defined as the time from Initial treatment to recurrence of tumor or death</description>
        <time_frame>assessed up to 5 years</time_frame>
        <population>Analysis population included LABC participants who achieved pathologic response (pCR). More appropriate PFS analysis for MBC cohort is presented elsewhere in these results.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort1: Stage IV HER-2 Overexpressing Metastatic Breast Cancer (MBC) Patients</title>
            <description>Pertuzumab administered as 840 mg IV during cycle 1 followed by 420 mg IV once every three weeks starting cycle 2.&#xD;
Trastuzumab loading dose of 4mg/kg IV for week one followed by 2mg/kg IV weekly.&#xD;
Nab-paclitaxel 100 mg/m2 IV weekly.&#xD;
Treatment is scheduled to continue until:&#xD;
Disease progression Unmanageable toxicity Primary physician or patient request to discontinue therapy Study termination by the sponsors</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: HER2+ Locally Advanced Breast Cancer (LABC) Patients</title>
            <description>Pertuzumab administered as 840 mg IV during cycle 1 followed by 420 mg IV once every three weeks starting cycle 2.&#xD;
Trastuzumab loading dose of 4mg/kg IV for week one followed by 2mg/kg IV weekly.&#xD;
Nab-paclitaxel 100 mg/m2 IV weekly.&#xD;
Treatment is scheduled to continue until:&#xD;
A planned 6 cycles Unmanageable toxicity Primary physician or patient request to discontinue therapy Study termination by the sponsors</description>
          </group>
        </group_list>
        <measure>
          <title>Five Year Disease-free Survival (LABC Cohort)</title>
          <description>Estimated using the method of Kaplan-Meier. Disease-free survival is defined as the time from Initial treatment to recurrence of tumor or death</description>
          <population>Analysis population included LABC participants who achieved pathologic response (pCR). More appropriate PFS analysis for MBC cohort is presented elsewhere in these results.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="96.3" lower_limit="76.5" upper_limit="99.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Response (MBC Cohort)</title>
        <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
        <time_frame>Up to 5 years</time_frame>
        <population>Overall response is not appropriate in the neoadjuvant or LABC cohort.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort1: Stage IV HER-2 Overexpressing Metastatic Breast Cancer (MBC) Patients</title>
            <description>Pertuzumab administered as 840 mg IV during cycle 1 followed by 420 mg IV once every three weeks starting cycle 2.&#xD;
Trastuzumab loading dose of 4mg/kg IV for week one followed by 2mg/kg IV weekly.&#xD;
Nab-paclitaxel 100 mg/m2 IV weekly.&#xD;
Treatment is scheduled to continue until:&#xD;
Disease progression Unmanageable toxicity Primary physician or patient request to discontinue therapy Study termination by the sponsors</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: HER2+ Locally Advanced Breast Cancer (LABC) Patients</title>
            <description>Pertuzumab administered as 840 mg IV during cycle 1 followed by 420 mg IV once every three weeks starting cycle 2.&#xD;
Trastuzumab loading dose of 4mg/kg IV for week one followed by 2mg/kg IV weekly.&#xD;
Nab-paclitaxel 100 mg/m2 IV weekly.&#xD;
Treatment is scheduled to continue until:&#xD;
A planned 6 cycles Unmanageable toxicity Primary physician or patient request to discontinue therapy Study termination by the sponsors</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response (MBC Cohort)</title>
          <description>Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
          <population>Overall response is not appropriate in the neoadjuvant or LABC cohort.</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="18"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Five Year Overall Survival</title>
        <description>Estimated by the Kaplan-Meier method. From the initial date of treatment to date of death from any cause.</description>
        <time_frame>Assessed up to 5 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort1: Stage IV HER-2 Overexpressing Metastatic Breast Cancer (MBC) Patients</title>
            <description>Pertuzumab administered as 840 mg IV during cycle 1 followed by 420 mg IV once every three weeks starting cycle 2.&#xD;
Trastuzumab loading dose of 4mg/kg IV for week one followed by 2mg/kg IV weekly.&#xD;
Nab-paclitaxel 100 mg/m2 IV weekly.&#xD;
Treatment is scheduled to continue until:&#xD;
Disease progression Unmanageable toxicity Primary physician or patient request to discontinue therapy Study termination by the sponsors</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2: HER2+ Locally Advanced Breast Cancer (LABC) Patients</title>
            <description>Pertuzumab administered as 840 mg IV during cycle 1 followed by 420 mg IV once every three weeks starting cycle 2.&#xD;
Trastuzumab loading dose of 4mg/kg IV for week one followed by 2mg/kg IV weekly.&#xD;
Nab-paclitaxel 100 mg/m2 IV weekly.&#xD;
Treatment is scheduled to continue until:&#xD;
A planned 6 cycles Unmanageable toxicity Primary physician or patient request to discontinue therapy Study termination by the sponsors</description>
          </group>
        </group_list>
        <measure>
          <title>Five Year Overall Survival</title>
          <description>Estimated by the Kaplan-Meier method. From the initial date of treatment to date of death from any cause.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.5" lower_limit="8.6" upper_limit="86.1"/>
                    <measurement group_id="O2" value="94.1" lower_limit="77.6" upper_limit="98.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were assessed from the time of initial treatment until 30 days post discontinuation of treatment, up to 5 years.</time_frame>
      <desc>&quot;Other Adverse Events&quot; include all events that were not severe adverse events regardless of grade or relation to treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Cohort1: Stage IV HER-2 Overexpressing Metastatic Breast Cancer (MBC) Patients</title>
          <description>Pertuzumab administered as 840 mg IV during cycle 1 followed by 420 mg IV once every three weeks starting cycle 2.&#xD;
Trastuzumab loading dose of 4mg/kg IV for week one followed by 2mg/kg IV weekly.&#xD;
Nab-paclitaxel 100 mg/m2 IV weekly.&#xD;
Treatment is scheduled to continue until:&#xD;
Disease progression Unmanageable toxicity Primary physician or patient request to discontinue therapy Study termination by the sponsors</description>
        </group>
        <group group_id="E2">
          <title>Cohort 2: HER2+ Locally Advanced Breast Cancer (LABC) Patients</title>
          <description>Pertuzumab administered as 840 mg IV during cycle 1 followed by 420 mg IV once every three weeks starting cycle 2.&#xD;
Trastuzumab loading dose of 4mg/kg IV for week one followed by 2mg/kg IV weekly.&#xD;
Nab-paclitaxel 100 mg/m2 IV weekly.&#xD;
Treatment is scheduled to continue until:&#xD;
A planned 6 cycles Unmanageable toxicity Primary physician or patient request to discontinue therapy Study termination by the sponsors</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Cardiac disorders - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Catheter related infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Oth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal di</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <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="18" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="45" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="162" subjects_affected="16" subjects_at_risk="18"/>
                <counts group_id="E2" events="172" subjects_affected="40" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac disorders - Other, specify</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Chest pain - cardiac</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="7" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="21" subjects_affected="6" subjects_at_risk="18"/>
                <counts group_id="E2" events="22" subjects_affected="7" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Tricuspid valve disease</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear and labyrinth disorders - Other, spe</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="4" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Hearing impaired</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Vestibular disorder</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="12" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="7" subjects_affected="3" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Eye disorders - Other, specify</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="6" subjects_affected="4" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Floaters</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Watering eyes</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E2" events="11" subjects_affected="7" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="12" subjects_affected="8" subjects_at_risk="18"/>
                <counts group_id="E2" events="34" subjects_affected="16" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="29" subjects_affected="10" subjects_at_risk="18"/>
                <counts group_id="E2" events="86" subjects_affected="31" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Esophageal ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="20" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" events="15" subjects_affected="5" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, spec</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="8" subjects_affected="6" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Gastrointestinal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Hemorrhoidal hemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Hemorrhoids</sub_title>
                <counts group_id="E1" events="23" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="22" subjects_affected="8" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="14" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E2" events="14" subjects_affected="8" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="24" subjects_affected="8" subjects_at_risk="18"/>
                <counts group_id="E2" events="68" subjects_affected="28" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Oral dysesthesia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Rectal hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Rectal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Salivary duct inflammation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Stomach pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="8" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E2" events="12" subjects_affected="10" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="62" subjects_affected="10" subjects_at_risk="18"/>
                <counts group_id="E2" events="39" subjects_affected="17" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Facial pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="120" subjects_affected="16" subjects_at_risk="18"/>
                <counts group_id="E2" events="183" subjects_affected="43" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="7" subjects_affected="5" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>General disorders and administration sit</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E2" events="9" subjects_affected="7" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="10" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E2" events="11" subjects_affected="6" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatobiliary disorders - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bladder infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Breast infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Eye infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Lip infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Nail infection</sub_title>
                <counts group_id="E1" events="8" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="13" subjects_affected="6" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Otitis externa</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" events="29" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E2" events="7" subjects_affected="5" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Rash pustular</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="4" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="12" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" events="12" subjects_affected="7" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="7" subjects_affected="5" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Vaginal infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Fracture</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Seroma</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Wound dehiscence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="27" subjects_affected="11" subjects_at_risk="18"/>
                <counts group_id="E2" events="79" subjects_affected="22" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="8" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" events="24" subjects_affected="9" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="44" subjects_affected="10" subjects_at_risk="18"/>
                <counts group_id="E2" events="62" subjects_affected="16" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Cholesterol high</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="7" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Lymphocyte count increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="29" subjects_affected="8" subjects_at_risk="18"/>
                <counts group_id="E2" events="26" subjects_affected="13" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" events="7" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Serum amylase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="10" subjects_affected="3" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="108" subjects_affected="14" subjects_at_risk="18"/>
                <counts group_id="E2" events="80" subjects_affected="27" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="10" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E2" events="17" subjects_affected="7" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Glucose intolerance</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="9" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="8" subjects_affected="3" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E2" events="14" subjects_affected="7" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="6" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="23" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E2" events="13" subjects_affected="7" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="29" subjects_affected="9" subjects_at_risk="18"/>
                <counts group_id="E2" events="18" subjects_affected="8" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" events="11" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="15" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E2" events="26" subjects_affected="12" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="13" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E2" events="33" subjects_affected="16" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="16" subjects_affected="8" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Oth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Obesity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="11" subjects_affected="5" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="6" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="12" subjects_affected="7" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="9" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" events="9" subjects_affected="3" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Chest wall pain</sub_title>
                <counts group_id="E1" events="20" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Muscle weakness lower limb</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue di</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="12" subjects_affected="7" subjects_at_risk="18"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="13" subjects_affected="8" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecif</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Tumor pain</sub_title>
                <counts group_id="E1" events="13" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cognitive disturbance</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="31" subjects_affected="13" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="18" subjects_affected="6" subjects_at_risk="18"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Nervous system disorders - Other, specif</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="7" subjects_affected="4" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="104" subjects_affected="15" subjects_at_risk="18"/>
                <counts group_id="E2" events="150" subjects_affected="36" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Spasticity</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="17" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E2" events="17" subjects_affected="8" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="8" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" events="11" subjects_affected="4" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="16" subjects_affected="6" subjects_at_risk="18"/>
                <counts group_id="E2" events="22" subjects_affected="8" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Psychiatric disorders - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Urinary tract pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Breast pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="10" subjects_affected="5" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Irregular menstruation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Menorrhagia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Reproductive system and breast disorders</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Vaginal dryness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" events="18" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="16" subjects_affected="6" subjects_at_risk="18"/>
                <counts group_id="E2" events="18" subjects_affected="10" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="12" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E2" events="17" subjects_affected="9" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="8" subjects_affected="6" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Postnasal drip</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal di</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E2" events="10" subjects_affected="4" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="73" subjects_affected="12" subjects_at_risk="18"/>
                <counts group_id="E2" events="42" subjects_affected="16" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="8" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E2" events="22" subjects_affected="10" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Erythema multiforme</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Nail discoloration</sub_title>
                <counts group_id="E1" events="37" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E2" events="38" subjects_affected="15" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Nail loss</sub_title>
                <counts group_id="E1" events="16" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="8" subjects_affected="3" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Nail ridging</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Pain of skin</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysesthesia syndro</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Periorbital edema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Photosensitivity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="9" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E2" events="19" subjects_affected="10" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" events="46" subjects_affected="9" subjects_at_risk="18"/>
                <counts group_id="E2" events="78" subjects_affected="24" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="9" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" events="24" subjects_affected="11" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders -</sub_title>
                <counts group_id="E1" events="30" subjects_affected="8" subjects_at_risk="18"/>
                <counts group_id="E2" events="30" subjects_affected="13" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Skin hyperpigmentation</sub_title>
                <counts group_id="E1" events="43" subjects_affected="8" subjects_at_risk="18"/>
                <counts group_id="E2" events="34" subjects_affected="12" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Skin hypopigmentation</sub_title>
                <counts group_id="E1" events="5" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Skin ulceration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E2" events="21" subjects_affected="6" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="122" subjects_affected="14" subjects_at_risk="18"/>
                <counts group_id="E2" events="148" subjects_affected="29" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Lymphedema</sub_title>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="45"/>
              </event>
              <event>
                <sub_title>Vascular disorders - Other, specify</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="45"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Paul Frankel, Ph.D.</name_or_title>
      <organization>City of Hope</organization>
      <phone>626-218-5265</phone>
      <email>pfrankel@coh.org</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/NCT01730833
org study id: 12147
secondary id: NCI-2012-02371
secondary id: R01CA166020
secondary id: AACR Grant 12-60-26-WANG
nct id: NCT01730833
lead sponsor: 
collaborator: 
has dmc: Yes
This phase II trial studies how well pertuzumab, trastuzumab, and paclitaxel
      albumin-stabilized nanoparticle formulation work in treating patients with human epidermal
      growth factor receptor (HER) 2-positive stage II-IV breast cancer. Monoclonal antibodies,
      such as pertuzumab and trastuzumab, can block tumor growth in different ways. Some block the
      ability of tumor cells to grow and spread. Others find tumor cells and help kill them or
      carry tumor-killing substances to them. Drugs used in chemotherapy, such as paclitaxel
      albumin-stabilized nanoparticle formulation, work in different ways to kill tumor cells or
      stop them from growing. Giving pertuzumab and trastuzumab together with paclitaxel
      albumin-stabilized nanoparticle formulation may be a better way to block tumor growth.
PRIMARY OBJECTIVES:

      I. To determine efficacy of administration of pertuzumab in combination with trastuzumab with
      nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) in subjects with
      stage IV human epidermal growth factor receptor (HER)-2 overexpressing metastatic breast
      cancer (MBC) as measured by progression free survival (PFS).

      II. To determine the efficacy as neoadjuvant treatment of the regimen in HER2+ locally
      advanced breast cancer (LABC) as defined by pathologic complete response (pCR).

      SECONDARY OBJECTIVES:

      I. To evaluate the safety of pertuzumab when added to trastuzumab and nab-paclitaxel in HER-2
      overexpressing MBC and LABC cancer as assessed by the frequency and severity of adverse
      events (AEs), abnormal findings on physical examination, laboratory tests, and vital signs.

      II. To evaluate the objective response rate (Response Evaluation Criteria in Solid Tumors
      [RECIST] 1.1) and duration of response in MBC.

      III. To evaluate the efficacy of the regimen by assessing tumor response including assessment
      of residual cancer burden (RCB) scores in LABC.

      IV. To assess the progression free survival (MBC), relapse-free survival (LABC) and overall
      survival in all patients.

      V. To perform exploratory circulatory gene, micro-ribonucleic acid (RNA), and exosome
      profiling as well as protein and glycomic profiling.

      VI. To assess the feasibility of molecular profiling in both primary and metastatic tumor
      samples.

      VII. To assess numerical and qualitative aspects of circulating tumor cells and circulating
      tumor-derived deoxyribonucleic acid (DNA).

      OUTLINE: Patients receive pertuzumab intravenously (IV) over 30-60 minutes on day 1,
      trastuzumab IV over 30-90 minutes and paclitaxel albumin-stabilized nanoparticle formulation
      IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days in the absence of
      disease progression or unacceptable toxicity (patients with MBC) or for 6 courses in the
      absence of disease progression or unacceptable toxicity (patients with LABC).

      After completion of study treatment, patients are followed up every 3 months for 4 years and
      then every 6 months for 1 year.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression Free Survival (MBC Cohort)
time frame: assessed up to 5 years
description: Estimated using the product-limit method of Kaplan and Meier. From time of initial treatment until disease progression or death. Progression is 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: Five Year Disease-free Survival (LABC Cohort)
time frame: assessed up to 5 years
description: Estimated using the method of Kaplan-Meier. Disease-free survival is defined as the time from Initial treatment to recurrence of tumor or death
measure: Overall Response (MBC Cohort)
time frame: Up to 5 years
description: Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
measure: Five Year Overall Survival
time frame: Assessed up to 5 years
description: Estimated by the Kaplan-Meier method. From the initial date of treatment to date of death from any cause.
arm group label: Treatment (pertuzumab, trastuzumab, nab-paclitaxel)
arm group type: Experimental
description: Patients receive pertuzumab IV over 30-60 minutes on day 1, trastuzumab IV over 30-90 minutes and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: pertuzumab
description: Given IV
arm group label: Treatment (pertuzumab, trastuzumab, nab-paclitaxel)
other name: 2C4 antibody
other name: monoclonal antibody 2C4
other name: Perjeta
other name: rhuMAb-2C4
intervention type: Biological
intervention name: trastuzumab
description: Given IV
arm group label: Treatment (pertuzumab, trastuzumab, nab-paclitaxel)
other name: anti-c-erB-2
other name: Herceptin
other name: MOAB HER2
intervention type: Drug
intervention name: paclitaxel albumin-stabilized nanoparticle formulation
description: Given IV
arm group label: Treatment (pertuzumab, trastuzumab, nab-paclitaxel)
other name: ABI-007
other name: nab paclitaxel
other name: nab-paclitaxel
other name: nanoparticle albumin-bound paclitaxel
intervention type: Other
intervention name: laboratory biomarker analysis
description: Optional correlative studies
arm group label: Treatment (pertuzumab, trastuzumab, nab-paclitaxel)
criteria: 
gender: Female
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Joanne Mortimer, MD
role: Principal Investigator
affiliation: City of Hope Medical Center
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Inflammatory Breast Neoplasms
mesh term: Paclitaxel
mesh term: Albumin-Bound Paclitaxel
mesh term: Trastuzumab
mesh term: Pertuzumab
mesh term: Antibodies
mesh term: Immunoglobulins
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 