<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/NCT03286842</url>
  </required_header>
  <id_info>
    <org_study_id>D0816C00018</org_study_id>
    <nct_id>NCT03286842</nct_id>
  </id_info>
  <brief_title>To Study Clinical Effectiveness and Safety of Olaparib Monotherapy in Metastatic Breast Cancer Patients.</brief_title>
  <official_title>A Phase IIIb, Single-arm, Open-label Multicentre Study of Olaparib Monotherapy in the Treatment of HER2-ve Metastatic Breast Cancer Patients With Germline or Somatic BRCA1/2 Mutations.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This open-label, multi-centre phase IIIb study will assess the effectiveness, benefits and&#xD;
      potential harms in the use of olaparib monotherapy treatment for patients with HER2-ve&#xD;
      metastatic breast cancer associated with germline or somatic breast cancer susceptibility&#xD;
      gene (gBRCA1/2 or sBRCA1/2) mutations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is a phase IIIb, multicenter, single-arm, open-label study designed to evaluate the&#xD;
      clinical effectiveness in a real-world setting of olaparib monotherapy in patients with&#xD;
      confirmed germline or somatic breast cancer susceptibility gene (gBRCA1/2 or sBRCA1/2)&#xD;
      mutations. This study will generate additional data to support other olaparib studies, which&#xD;
      may help inform and guide clinical practice. Physician defined the progression-free survival&#xD;
      (PFS) for gBRCAm patients is the primary outcome measure. Based on the prevalence of gBRCA1/2&#xD;
      mutations, it is estimated that up to 1400 patients may require screening in order to&#xD;
      identify 250 gBRCA mutated patients and 20 sBRCA mutated patients. Patients will be&#xD;
      administered two olaparib 150mg tablets in morning and evening of every day after a light&#xD;
      meal. Dose reductions may be required for olaparib treatment related toxicities. Patients&#xD;
      should continue to receive study treatment until documented physician-defined disease&#xD;
      progression as assessed by the investigator (gBRCA mutated patients), RECIST1.1 disease&#xD;
      progression (sBRCA mutated patients) or unacceptable toxicity, or for as long as they do not&#xD;
      meet any other discontinuation criteria. A positive benefit/risk profile is expected and no&#xD;
      ethical issues are identified from exposing patients to olaparib within the planned clinical&#xD;
      study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 17, 2018</start_date>
  <completion_date type="Actual">October 8, 2021</completion_date>
  <primary_completion_date type="Actual">October 8, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</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 (PFS) in Real-world Setting in Germline BRCA Mutated Participants</measure>
    <time_frame>At every visit until the earliest of disease progression, death or end of study (up to 3 years)</time_frame>
    <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting through assessment of PFS in germline BRCA mutated patients was evaluated. PFS is defined as the time from first dose of olaparib to the date of progression or death from any cause. In this study, disease progression in gBRCAm patients will be based on Investigator assessment, i.e. radiological ( e.g. RECIST) progression, symptomatic progression, or clear progression of non-measurable disease, as long as progression can be documented.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) in Germline BRCA Mutated Participants</measure>
    <time_frame>At every visit and until death or end of study (up to 3 years)</time_frame>
    <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of overall survival in germline BRCA mutated participants was determined. OS is defined as the time from first dose of olaparib to the date of death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First Subsequent Treatment or Death (TFST) in Germline BRCA Mutated Participants</measure>
    <time_frame>At every visit until start of first subsequent anticancer treatment or death or end of study (up to 3 years)</time_frame>
    <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. TFST is defined as the time from first dose of olaparib to first subsequent treatment commencement or death if this occurs before commencement of first subsequent treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Second Subsequent Treatment or Death (TSST) in Germline BRCA Mutated Participants</measure>
    <time_frame>At every visit until start of second subsequent anticancer treatment or death or end of study (up to 3 years)</time_frame>
    <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. TSST is defined as the time from first dose of olaparib to second subsequent treatment commencement or death if this occurs before commencement of second subsequent treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Study Treatment Discontinuation or Death (TDT) in Germline BRCA Mutated Participants</measure>
    <time_frame>At every visit and until discontinuation of study treatment or death or end of study (up to 3 years)</time_frame>
    <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated patients was determined. TDT is defined as the time from first dose of olaparib to study treatment discontinuation or death if this occurs before discontinuation of study treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Second Progression or Death (PFS2) in Germline BRCA Mutated Participants</measure>
    <time_frame>At every visit until second progression or death or end of study (up to 3 years)</time_frame>
    <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. PFS2 is defined as the time from first dose of olaparib to the earliest progression event subsequent to that used for the primary variable PFS or death from any cause. Patients alive and for whom a second disease progression has not been observed will be censored at the last time known to be alive and without a second disease progression. In this study, disease progression in gBRCAm patients will be based on Investigator assessment, i.e. radiological ( e.g. RECIST) progression, symptomatic progression, or clear progression of non-measurable disease, as long as progression can be documented</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Response Rate (CRR) in Germline BRCA Mutated Participants</measure>
    <time_frame>At every visit until disease progression or death or end of study (up to 3 years)</time_frame>
    <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of clinical response rate and duration of clinical response in germline BRCA mutated participants was determined. CRR is defined as the percentage of patients assessed by the Investigator as responding. Response in gBRCAm patients were based on the Investigator's assessment. Data obtained up until progression, or last evaluable assessment in the absence of progression, will be included in the assessment of CRR. However, any responses, which occurred after a further anticancer therapy was received, will not be included in the numerator for the CRR calculation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Clinical Response (DoCR) in Germline BRCA Mutated Participants</measure>
    <time_frame>At every visit until disease progression or death or end of study (up to 3 years)</time_frame>
    <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of clinical response rate and duration of clinical response in germline BRCA mutated participants was determined. DoCR is defined as the time from the date the Investigator first assessed the patient as responding to the date the Investigator assessed the patient as progressing or the date of death from any cause. The end of response should coincide with the date of progression or death used for the PFS endpoint. The time of the initial response will be defined as the latest of the dates contributing towards the first visit response. If a patient does not progress following a response, they will be censored at the PFS censoring date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>From Screening (Day -28 to Day -1) until post DCO [up to 3 years]</time_frame>
    <description>The safety and tolerability of olaparib treatment in HER2-ve metastatic breast cancer patients in a real-word setting was evaluated.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">256</enrollment>
  <condition>HER2-ve Metastatic Breast Cancer</condition>
  <condition>Germline BRCA1/2 Mutations</condition>
  <condition>Somatic BRCA1/2 Mutations</condition>
  <arm_group>
    <arm_group_label>Olaparib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Olaparib 150mg tablets administered orally twice daily continuously</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olaparib</intervention_name>
    <description>Patients will be administered olaparib orally, twice daily at 300 mg. Two (2) 150 mg olaparib tablets should be taken at the same time each morning and evening of every day, approximately 12 hours apart.</description>
    <arm_group_label>Olaparib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Provision of informed consent prior to any study specific procedures. For patients&#xD;
             aged &lt;20 years and screened in Japan, a written informed consent should be obtained&#xD;
             from the patient and his or her legally acceptable representative.&#xD;
&#xD;
          2. Patients must be ≥18 years of age.&#xD;
&#xD;
          3. Histologically or cytologically confirmed HER2-ve breast cancer with evidence of&#xD;
             metastatic disease. Patients can have either TNBC (defined as oestrogen receptor and&#xD;
             progesterone receptor negative [immunohistochemistry nuclear staining &lt;1%] and HER2-ve&#xD;
             [immunohistochemistry 0, 1+ or 2+ and/or in situ hybridization nonamplified with ratio&#xD;
             less than 2.0]) or oestrogen receptor / progesterone receptor positive breast cancer&#xD;
             as long as they are HER2-ve.&#xD;
&#xD;
          4. Documented BRCA1/2 status&#xD;
&#xD;
               -  To be regarded as BRCA1/2 (+ve), the patient must have a mutation that is&#xD;
                  predicted to be deleterious or suspected deleterious (known or predicted to be&#xD;
                  detrimental / lead to loss of function). Mutations that are not clearly&#xD;
                  pathogenic may be assessed by a committee of genetic specialists to adjudicate if&#xD;
                  the patient is eligible.&#xD;
&#xD;
               -  Patients with tBRCA mutations: must be confirmed by a validated method (e.g.&#xD;
                  results from a CLIA-certified laboratory or CE-IVD device)&#xD;
&#xD;
          5. Prior treatment with a taxane or an anthracycline in either an adjuvant (may include&#xD;
             neoadjuvant) or metastatic breast cancer treatment setting.&#xD;
&#xD;
          6. Patients should have received no more than two prior cytotoxic chemotherapy regimens&#xD;
             in the metastatic setting. If a patient has oestrogen receptor and/or progesterone&#xD;
             receptor positive HER2 negative metastatic breast cancer and has completed a prior&#xD;
             line of hormonal treatment, then if the current or currently planned choice of&#xD;
             treatment for the patient does not include a hormonal treatment then they would be a&#xD;
             suitable patient to enter the study. Previous endocrine therapy could be in either an&#xD;
             adjuvant or a metastatic setting and include endocrine therapy in combination with a&#xD;
             targeted agent such as a CDK4/6 or mTOR inhibitor.&#xD;
&#xD;
          7. Be considered suitable, by the Investigator, for further treatment with single-agent&#xD;
             chemotherapy for the metastatic disease&#xD;
&#xD;
          8. Patients must have normal organ and bone marrow function measured within 14 days prior&#xD;
             to administration of study treatment as defined below:&#xD;
&#xD;
               -  Haemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L&#xD;
&#xD;
               -  Platelet count ≥ 100 x 109/L&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) unless the&#xD;
                  patient has documented Gilbert's Syndrome&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT))&#xD;
                  / alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase (SGPT)) ≤&#xD;
                  2.5 x institutional ULN unless liver metastases are present in which case they&#xD;
                  must be ≤ 5x ULN&#xD;
&#xD;
               -  Patients must have creatinine clearance (CrCl) estimated using the Cockcroft-&#xD;
                  Gault equation of ≥ 51 mL/min or 24 hour urine test may be done if standard of&#xD;
                  care:&#xD;
&#xD;
             Estimated CrCl = (140-age [years]) x weight (kg) (x F)a serum creatinine (mg/dL) x 72&#xD;
&#xD;
             a- where F=0.85 for females and F=1 for males&#xD;
&#xD;
          9. Patients must have a life expectancy ≥ 16 weeks&#xD;
&#xD;
         10. Postmenopausal or evidence of non-childbearing status for women of childbearing&#xD;
             potential: negative urine or serum pregnancy test within 28 days of study treatment&#xD;
             and confirmed prior to treatment on Day 1&#xD;
&#xD;
             Postmenopausal is defined as (at least one criterion met):&#xD;
&#xD;
               -  amenorrhoeic for 1 year or more following cessation of exogenous hormonal&#xD;
                  treatments&#xD;
&#xD;
               -  luteinizing hormone and follicle stimulating hormone levels in the postmenopausal&#xD;
                  range for women under 50&#xD;
&#xD;
               -  radiation-induced oophorectomy with last menses &gt;1 year ago&#xD;
&#xD;
               -  chemotherapy-induced menopause with &gt;1 year interval since last menses&#xD;
&#xD;
               -  surgical sterilisation (bilateral oophorectomy or hysterectomy).&#xD;
&#xD;
         11. Women of childbearing potential, who are sexually active, must agree to the use of one&#xD;
             highly effective form of contraception and their male partners must use a condom from&#xD;
             the signing of the informed consent, throughout the period of taking study treatment&#xD;
             and for at least 1 month after last dose of study drug, or they must totally/truly&#xD;
             abstain from any form of sexual intercourse.&#xD;
&#xD;
         12. Male patients must use a condom during treatment and for 3 months after the last dose&#xD;
             of olaparib when having sexual intercourse with a pregnant woman or with a woman of&#xD;
             childbearing potential. Female partners of male patients should also use one highly&#xD;
             effective form of contraception if they are of childbearing potential.&#xD;
&#xD;
         13. Patient is willing and able to comply with the protocol for the duration of the study&#xD;
             including undergoing treatment and scheduled visits and examinations for greater than&#xD;
             6 months.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca&#xD;
             staff and/or staff at the study site)&#xD;
&#xD;
          2. Previous enrolment in the present study&#xD;
&#xD;
          3. Exposure to an investigational product (IP) during the last 1 month or 5 half-lives&#xD;
             (whichever is longer) prior to enrolment&#xD;
&#xD;
          4. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative&#xD;
             reasons) within 3 weeks prior to study treatment&#xD;
&#xD;
          5. Any previous treatment with a PARP inhibitor, including olaparib&#xD;
&#xD;
          6. Other malignancy unless curatively treated with no evidence of disease for ≥5 years&#xD;
             except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer&#xD;
             of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial&#xD;
             carcinoma.&#xD;
&#xD;
          7. Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as&#xD;
             judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic&#xD;
             arrhythmia, congestive heart failure, QTcF prolongation &gt;500 ms, electrolyte&#xD;
             disturbances, etc.), or patients with congenital long QT syndrome.&#xD;
&#xD;
          8. Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin,&#xD;
             clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,&#xD;
             saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g.,&#xD;
             ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout&#xD;
             period prior to starting olaparib is 2 weeks.&#xD;
&#xD;
          9. Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin,&#xD;
             rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or&#xD;
             moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout&#xD;
             period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3&#xD;
             weeks for other agents.&#xD;
&#xD;
         10. Persistent toxicities (&gt;Common Terminology Criteria for Adverse Event (CTCAE) grade 2)&#xD;
             caused by previous cancer therapy, excluding alopecia.&#xD;
&#xD;
         11. Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with&#xD;
             features suggestive of MDS/AML&#xD;
&#xD;
         12. Patients with symptomatic uncontrolled brain metastases.&#xD;
&#xD;
             - Exception: Patients with adequately treated brain metastases documented by baseline&#xD;
             CT or MRI scan that has not progressed since previous scans and that does not require&#xD;
             corticosteroids (except ≤10 mg/day prednisone or equivalent for at least 14 continuous&#xD;
             days prior to dosing) for management of CNS symptoms are eligible, provided that a&#xD;
             repeat CT or MRI following the identification of CNS metastases (obtained at least 2&#xD;
             weeks after definitive therapy) must document adequately treated brain metastases.&#xD;
&#xD;
         13. Major surgery within 2 weeks of starting study treatment and patients must have&#xD;
             recovered from any effects of any major surgery.&#xD;
&#xD;
         14. Patients considered a poor medical risk due to a serious, uncontrolled medical&#xD;
             disorder, non-malignant systemic disease or active, uncontrolled infection.&#xD;
&#xD;
             Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent&#xD;
             (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable&#xD;
             spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral&#xD;
             lung disease on high resolution computed tomography (HRCT) scan or any psychiatric&#xD;
             disorder that prohibits obtaining informed consent.&#xD;
&#xD;
         15. Patients unable to swallow orally administered medication and patients with&#xD;
             gastrointestinal disorders likely to interfere with absorption of the study medication&#xD;
&#xD;
         16. Breastfeeding women&#xD;
&#xD;
         17. Immunocompromised patients, e.g., patients who are known to be serologically positive&#xD;
             for human immunodeficiency virus (HIV)&#xD;
&#xD;
         18. Patients with a known hypersensitivity to olaparib or any of the excipients of the&#xD;
             product&#xD;
&#xD;
         19. Patients with known active hepatitis (i.e., hepatitis B or C)&#xD;
&#xD;
         20. Whole blood transfusions in the last 28 days prior to entry to the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>130 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Karen Gelmon, MD, FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>BritishColumbiaCancerAgency, 600W.10th Ave,Vancouver,Canada.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Towson</city>
        <state>Maryland</state>
        <zip>21204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Plovdiv</city>
        <zip>4004</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sofia</city>
        <zip>1303</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sofia</city>
        <zip>1330</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Varna</city>
        <zip>9000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 4E6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Quebec City</city>
        <state>Quebec</state>
        <zip>G1S 4L8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Angers Cedex 02</city>
        <zip>49055</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Avignon</city>
        <zip>84000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Besançon</city>
        <zip>25000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Caen cedex 05</city>
        <zip>14076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Le Mans</city>
        <zip>72000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lille</city>
        <zip>59000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Limoges</city>
        <zip>87042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lorient cedex</city>
        <zip>56322</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Marseille</city>
        <zip>13273</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Montpellier</city>
        <zip>34070</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nancy</city>
        <zip>54100</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nantes</city>
        <zip>44202</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>London</city>
        <zip>SW3 6JJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sutton</city>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Australia</country>
    <country>China</country>
  </removed_countries>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;amp;parentIdentifier=D0816C00018&amp;amp;attachmentIdentifier=aef63c74-06df-40d3-abe9-b750920e9fa5&amp;amp;fileName=D0816C00018_CSP_30Nov2020_Redacted.pdf&amp;amp;versionIdentifier=</url>
    <description>CSP_redacted</description>
  </link>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;amp;parentIdentifier=D0816C00018&amp;amp;attachmentIdentifier=c5f3b35e-e777-40b3-9b87-c363966f11d8&amp;amp;fileName=D0816C00018_SAP_30Nov2020_Redacted.pdf&amp;amp;versionIdentifier=</url>
    <description>SAP_redacted</description>
  </link>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;amp;parentIdentifier=D0816C00018&amp;amp;attachmentIdentifier=bf42d8ab-9b06-40de-a996-38cd1a8317d8&amp;amp;fileName=D0816C00018_Redacted_CSRSynopsis.pdf&amp;amp;versionIdentifier=</url>
    <description>Related Info</description>
  </link>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>August 17, 2017</study_first_submitted>
  <study_first_submitted_qc>September 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 19, 2017</study_first_posted>
  <results_first_submitted>October 7, 2022</results_first_submitted>
  <results_first_submitted_qc>December 22, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">January 17, 2023</results_first_posted>
  <last_update_submitted>December 22, 2022</last_update_submitted>
  <last_update_submitted_qc>December 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HER2-ve metastatic breast cancer</keyword>
  <keyword>Germline BRCA1/2 mutations</keyword>
  <keyword>Somatic BRCA1/2 mutations</keyword>
  <keyword>BRCA1</keyword>
  <keyword>BRCA2</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Olaparib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_time_frame>
    <ipd_access_criteria>When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_access_criteria>
    <ipd_url>https://astrazenecagroup-dt.pharmacm.com/DT/Home</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 19, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/42/NCT03286842/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 14, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/42/NCT03286842/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled in this study from 17-January-2018 to 21-March-2019 in 125 sites in 15 countries.</recruitment_details>
      <pre_assignment_details>Participants who met the inclusion and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment. A total of 256 participants were enrolled in this study but, only 255 started treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Olaparib</title>
          <description>Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="255"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="175"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="80"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Patients rolled over to another study</title>
              <participants_list>
                <participants group_id="P1" count="80"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment.</population>
      <group_list>
        <group group_id="B1">
          <title>Olaparib</title>
          <description>Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="255"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>The number analyzed in both the rows sums up to the overall number.</population>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Germline BRCA1/2 mutation (gBRCAm) cohort</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="252"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46.2" spread="11.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Somatic BRCA1/2 mutation (sBRCAm) cohort</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55.3" spread="13.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>The number analyzed in both the rows sums up to the overall number.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>gBRCAm cohort</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="252"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="248"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>sBRCAm cohort</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <population>The number analyzed in both the rows sums up to the overall number.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>gBRCAm cohort</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="252"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="189"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>sBRCAm cohort</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <population>The number analyzed in both the rows sums up to the overall number.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>gBRCAm cohort</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="252"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="177"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>sBRCAm cohort</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Progression-free Survival (PFS) in Real-world Setting in Germline BRCA Mutated Participants</title>
        <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting through assessment of PFS in germline BRCA mutated patients was evaluated. PFS is defined as the time from first dose of olaparib to the date of progression or death from any cause. In this study, disease progression in gBRCAm patients will be based on Investigator assessment, i.e. radiological ( e.g. RECIST) progression, symptomatic progression, or clear progression of non-measurable disease, as long as progression can be documented.</description>
        <time_frame>At every visit until the earliest of disease progression, death or end of study (up to 3 years)</time_frame>
        <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.</population>
        <group_list>
          <group group_id="O1">
            <title>Olaparib gBRCAm Cohort</title>
            <description>Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS) in Real-world Setting in Germline BRCA Mutated Participants</title>
          <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting through assessment of PFS in germline BRCA mutated patients was evaluated. PFS is defined as the time from first dose of olaparib to the date of progression or death from any cause. In this study, disease progression in gBRCAm patients will be based on Investigator assessment, i.e. radiological ( e.g. RECIST) progression, symptomatic progression, or clear progression of non-measurable disease, as long as progression can be documented.</description>
          <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.</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="252"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.18" lower_limit="6.97" upper_limit="9.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS) in Germline BRCA Mutated Participants</title>
        <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of overall survival in germline BRCA mutated participants was determined. OS is defined as the time from first dose of olaparib to the date of death from any cause.</description>
        <time_frame>At every visit and until death or end of study (up to 3 years)</time_frame>
        <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.</population>
        <group_list>
          <group group_id="O1">
            <title>Olaparib gBRCAm Cohort</title>
            <description>Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) in Germline BRCA Mutated Participants</title>
          <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of overall survival in germline BRCA mutated participants was determined. OS is defined as the time from first dose of olaparib to the date of death from any cause.</description>
          <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.</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="252"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.94" lower_limit="21.06" upper_limit="28.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to First Subsequent Treatment or Death (TFST) in Germline BRCA Mutated Participants</title>
        <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. TFST is defined as the time from first dose of olaparib to first subsequent treatment commencement or death if this occurs before commencement of first subsequent treatment.</description>
        <time_frame>At every visit until start of first subsequent anticancer treatment or death or end of study (up to 3 years)</time_frame>
        <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.</population>
        <group_list>
          <group group_id="O1">
            <title>Olaparib gBRCAm Cohort</title>
            <description>Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First Subsequent Treatment or Death (TFST) in Germline BRCA Mutated Participants</title>
          <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. TFST is defined as the time from first dose of olaparib to first subsequent treatment commencement or death if this occurs before commencement of first subsequent treatment.</description>
          <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.</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="252"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.40" lower_limit="8.61" upper_limit="10.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Second Subsequent Treatment or Death (TSST) in Germline BRCA Mutated Participants</title>
        <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. TSST is defined as the time from first dose of olaparib to second subsequent treatment commencement or death if this occurs before commencement of second subsequent treatment.</description>
        <time_frame>At every visit until start of second subsequent anticancer treatment or death or end of study (up to 3 years)</time_frame>
        <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.</population>
        <group_list>
          <group group_id="O1">
            <title>Olaparib gBRCAm Cohort</title>
            <description>Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Second Subsequent Treatment or Death (TSST) in Germline BRCA Mutated Participants</title>
          <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. TSST is defined as the time from first dose of olaparib to second subsequent treatment commencement or death if this occurs before commencement of second subsequent treatment.</description>
          <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.</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="252"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.72" lower_limit="13.50" upper_limit="17.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Study Treatment Discontinuation or Death (TDT) in Germline BRCA Mutated Participants</title>
        <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated patients was determined. TDT is defined as the time from first dose of olaparib to study treatment discontinuation or death if this occurs before discontinuation of study treatment.</description>
        <time_frame>At every visit and until discontinuation of study treatment or death or end of study (up to 3 years)</time_frame>
        <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.</population>
        <group_list>
          <group group_id="O1">
            <title>Olaparib gBRCAm Cohort</title>
            <description>Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Study Treatment Discontinuation or Death (TDT) in Germline BRCA Mutated Participants</title>
          <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated patients was determined. TDT is defined as the time from first dose of olaparib to study treatment discontinuation or death if this occurs before discontinuation of study treatment.</description>
          <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.</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="252"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.98" lower_limit="6.90" upper_limit="8.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Second Progression or Death (PFS2) in Germline BRCA Mutated Participants</title>
        <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. PFS2 is defined as the time from first dose of olaparib to the earliest progression event subsequent to that used for the primary variable PFS or death from any cause. Patients alive and for whom a second disease progression has not been observed will be censored at the last time known to be alive and without a second disease progression. In this study, disease progression in gBRCAm patients will be based on Investigator assessment, i.e. radiological ( e.g. RECIST) progression, symptomatic progression, or clear progression of non-measurable disease, as long as progression can be documented</description>
        <time_frame>At every visit until second progression or death or end of study (up to 3 years)</time_frame>
        <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.</population>
        <group_list>
          <group group_id="O1">
            <title>Olaparib gBRCAm Cohort</title>
            <description>Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Second Progression or Death (PFS2) in Germline BRCA Mutated Participants</title>
          <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. PFS2 is defined as the time from first dose of olaparib to the earliest progression event subsequent to that used for the primary variable PFS or death from any cause. Patients alive and for whom a second disease progression has not been observed will be censored at the last time known to be alive and without a second disease progression. In this study, disease progression in gBRCAm patients will be based on Investigator assessment, i.e. radiological ( e.g. RECIST) progression, symptomatic progression, or clear progression of non-measurable disease, as long as progression can be documented</description>
          <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.</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="252"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.49" lower_limit="13.17" upper_limit="17.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Response Rate (CRR) in Germline BRCA Mutated Participants</title>
        <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of clinical response rate and duration of clinical response in germline BRCA mutated participants was determined. CRR is defined as the percentage of patients assessed by the Investigator as responding. Response in gBRCAm patients were based on the Investigator's assessment. Data obtained up until progression, or last evaluable assessment in the absence of progression, will be included in the assessment of CRR. However, any responses, which occurred after a further anticancer therapy was received, will not be included in the numerator for the CRR calculation.</description>
        <time_frame>At every visit until disease progression or death or end of study (up to 3 years)</time_frame>
        <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Olaparib gBRCAm Cohort</title>
            <description>Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Response Rate (CRR) in Germline BRCA Mutated Participants</title>
          <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of clinical response rate and duration of clinical response in germline BRCA mutated participants was determined. CRR is defined as the percentage of patients assessed by the Investigator as responding. Response in gBRCAm patients were based on the Investigator's assessment. Data obtained up until progression, or last evaluable assessment in the absence of progression, will be included in the assessment of CRR. However, any responses, which occurred after a further anticancer therapy was received, will not be included in the numerator for the CRR calculation.</description>
          <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment.</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="252"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.6" lower_limit="43.3" upper_limit="55.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Clinical Response (DoCR) in Germline BRCA Mutated Participants</title>
        <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of clinical response rate and duration of clinical response in germline BRCA mutated participants was determined. DoCR is defined as the time from the date the Investigator first assessed the patient as responding to the date the Investigator assessed the patient as progressing or the date of death from any cause. The end of response should coincide with the date of progression or death used for the PFS endpoint. The time of the initial response will be defined as the latest of the dates contributing towards the first visit response. If a patient does not progress following a response, they will be censored at the PFS censoring date.</description>
        <time_frame>At every visit until disease progression or death or end of study (up to 3 years)</time_frame>
        <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Olaparib gBRCAm Cohort</title>
            <description>Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Clinical Response (DoCR) in Germline BRCA Mutated Participants</title>
          <description>The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of clinical response rate and duration of clinical response in germline BRCA mutated participants was determined. DoCR is defined as the time from the date the Investigator first assessed the patient as responding to the date the Investigator assessed the patient as progressing or the date of death from any cause. The end of response should coincide with the date of progression or death used for the PFS endpoint. The time of the initial response will be defined as the latest of the dates contributing towards the first visit response. If a patient does not progress following a response, they will be censored at the PFS censoring date.</description>
          <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="252"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.0" lower_limit="4.2" upper_limit="18.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</title>
        <description>The safety and tolerability of olaparib treatment in HER2-ve metastatic breast cancer patients in a real-word setting was evaluated.</description>
        <time_frame>From Screening (Day -28 to Day -1) until post DCO [up to 3 years]</time_frame>
        <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.</population>
        <group_list>
          <group group_id="O1">
            <title>Olaparib gBRCAm Cohort</title>
            <description>Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.</description>
          </group>
          <group group_id="O2">
            <title>Olaparib sBRCAm Cohort</title>
            <description>Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</title>
          <description>The safety and tolerability of olaparib treatment in HER2-ve metastatic breast cancer patients in a real-word setting was evaluated.</description>
          <population>The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.</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="252"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="243"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any AE casually related to study treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="214"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any AE of CTCAE grade 3 or higher</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="69"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any AE of CTCAE grade 3 or higher, causally related to study treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any AE with outcome = death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any AE with outcome = death, causally related to study treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any SAE (including events with outcome = death)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any SAE (including events with outcome = death), causally related to study treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any AE leading to discontinuation of study treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any AE leading to discontinuation of study treatment, causally related to study treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From Screening (Day -28 to -1) until post DCO [up to 3 years].</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Olaparib gBRCAm Cohort</title>
          <description>Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.</description>
        </group>
        <group group_id="E2">
          <title>Olaparib sBRCAm Cohort</title>
          <description>Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA v24.0</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="140" subjects_at_risk="252"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="32" subjects_at_risk="252"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="10" subjects_affected="7" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pancytopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Ileus paralytic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pancreatitis acute</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abscess</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>COVID-19 pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Chest wall abscess</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>H1N1 influenza</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Radiation necrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Spinal compression fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Spinal fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>General physical condition abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="252"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Bladder cancer stage 0, with cancer in situ</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Myelodysplastic syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pancreatic carcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Psychiatric decompensation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Lung disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pleurisy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA v24.0</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="243" subjects_at_risk="252"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="168" subjects_affected="98" subjects_at_risk="252"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="37" subjects_affected="22" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="71" subjects_affected="41" subjects_at_risk="252"/>
                <counts group_id="E2" events="6" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="25" subjects_affected="21" subjects_at_risk="252"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="31" subjects_affected="19" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="37" subjects_affected="30" subjects_at_risk="252"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="72" subjects_affected="53" subjects_at_risk="252"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="30" subjects_affected="25" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="236" subjects_affected="140" subjects_at_risk="252"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="111" subjects_affected="67" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="94" subjects_affected="70" subjects_at_risk="252"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="84" subjects_affected="59" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="43" subjects_affected="31" subjects_at_risk="252"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="17" subjects_affected="14" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="14" subjects_affected="13" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="22" subjects_affected="16" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="18" subjects_affected="14" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="36" subjects_affected="31" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </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="55" subjects_affected="39" subjects_at_risk="252"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="32" subjects_affected="28" subjects_at_risk="252"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="17" subjects_affected="17" subjects_at_risk="252"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="24" subjects_affected="21" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="28" subjects_affected="23" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="18" subjects_affected="16" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="103" subjects_affected="47" subjects_at_risk="252"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="15" subjects_affected="15" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="40" subjects_affected="35" subjects_at_risk="252"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="24" subjects_affected="21" subjects_at_risk="252"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>This document contains trade secrets and confidential commercial information, disclosure of which is prohibited without providing advance notice to AstraZeneca and opportunity to object.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Global Clinical Lead</name_or_title>
      <organization>AstraZeneca Clinical Study Information Center</organization>
      <phone>1-877-240-9479</phone>
      <email>information.center@astrazeneca.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03286842
org study id: D0816C00018
nct id: NCT03286842
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This open-label, multi-centre phase IIIb study will assess the effectiveness, benefits and
      potential harms in the use of olaparib monotherapy treatment for patients with HER2-ve
      metastatic breast cancer associated with germline or somatic breast cancer susceptibility
      gene (gBRCA1/2 or sBRCA1/2) mutations.
The study is a phase IIIb, multicenter, single-arm, open-label study designed to evaluate the
      clinical effectiveness in a real-world setting of olaparib monotherapy in patients with
      confirmed germline or somatic breast cancer susceptibility gene (gBRCA1/2 or sBRCA1/2)
      mutations. This study will generate additional data to support other olaparib studies, which
      may help inform and guide clinical practice. Physician defined the progression-free survival
      (PFS) for gBRCAm patients is the primary outcome measure. Based on the prevalence of gBRCA1/2
      mutations, it is estimated that up to 1400 patients may require screening in order to
      identify 250 gBRCA mutated patients and 20 sBRCA mutated patients. Patients will be
      administered two olaparib 150mg tablets in morning and evening of every day after a light
      meal. Dose reductions may be required for olaparib treatment related toxicities. Patients
      should continue to receive study treatment until documented physician-defined disease
      progression as assessed by the investigator (gBRCA mutated patients), RECIST1.1 disease
      progression (sBRCA mutated patients) or unacceptable toxicity, or for as long as they do not
      meet any other discontinuation criteria. A positive benefit/risk profile is expected and no
      ethical issues are identified from exposing patients to olaparib within the planned clinical
      study.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free Survival (PFS) in Real-world Setting in Germline BRCA Mutated Participants
time frame: At every visit until the earliest of disease progression, death or end of study (up to 3 years)
description: The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting through assessment of PFS in germline BRCA mutated patients was evaluated. PFS is defined as the time from first dose of olaparib to the date of progression or death from any cause. In this study, disease progression in gBRCAm patients will be based on Investigator assessment, i.e. radiological ( e.g. RECIST) progression, symptomatic progression, or clear progression of non-measurable disease, as long as progression can be documented.
measure: Overall Survival (OS) in Germline BRCA Mutated Participants
time frame: At every visit and until death or end of study (up to 3 years)
description: The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of overall survival in germline BRCA mutated participants was determined. OS is defined as the time from first dose of olaparib to the date of death from any cause.
measure: Time to First Subsequent Treatment or Death (TFST) in Germline BRCA Mutated Participants
time frame: At every visit until start of first subsequent anticancer treatment or death or end of study (up to 3 years)
description: The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. TFST is defined as the time from first dose of olaparib to first subsequent treatment commencement or death if this occurs before commencement of first subsequent treatment.
measure: Time to Second Subsequent Treatment or Death (TSST) in Germline BRCA Mutated Participants
time frame: At every visit until start of second subsequent anticancer treatment or death or end of study (up to 3 years)
description: The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. TSST is defined as the time from first dose of olaparib to second subsequent treatment commencement or death if this occurs before commencement of second subsequent treatment.
measure: Time to Study Treatment Discontinuation or Death (TDT) in Germline BRCA Mutated Participants
time frame: At every visit and until discontinuation of study treatment or death or end of study (up to 3 years)
description: The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated patients was determined. TDT is defined as the time from first dose of olaparib to study treatment discontinuation or death if this occurs before discontinuation of study treatment.
measure: Time to Second Progression or Death (PFS2) in Germline BRCA Mutated Participants
time frame: At every visit until second progression or death or end of study (up to 3 years)
description: The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. PFS2 is defined as the time from first dose of olaparib to the earliest progression event subsequent to that used for the primary variable PFS or death from any cause. Patients alive and for whom a second disease progression has not been observed will be censored at the last time known to be alive and without a second disease progression. In this study, disease progression in gBRCAm patients will be based on Investigator assessment, i.e. radiological ( e.g. RECIST) progression, symptomatic progression, or clear progression of non-measurable disease, as long as progression can be documented
measure: Clinical Response Rate (CRR) in Germline BRCA Mutated Participants
time frame: At every visit until disease progression or death or end of study (up to 3 years)
description: The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of clinical response rate and duration of clinical response in germline BRCA mutated participants was determined. CRR is defined as the percentage of patients assessed by the Investigator as responding. Response in gBRCAm patients were based on the Investigator's assessment. Data obtained up until progression, or last evaluable assessment in the absence of progression, will be included in the assessment of CRR. However, any responses, which occurred after a further anticancer therapy was received, will not be included in the numerator for the CRR calculation.
measure: Duration of Clinical Response (DoCR) in Germline BRCA Mutated Participants
time frame: At every visit until disease progression or death or end of study (up to 3 years)
description: The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of clinical response rate and duration of clinical response in germline BRCA mutated participants was determined. DoCR is defined as the time from the date the Investigator first assessed the patient as responding to the date the Investigator assessed the patient as progressing or the date of death from any cause. The end of response should coincide with the date of progression or death used for the PFS endpoint. The time of the initial response will be defined as the latest of the dates contributing towards the first visit response. If a patient does not progress following a response, they will be censored at the PFS censoring date.
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: From Screening (Day -28 to Day -1) until post DCO [up to 3 years]
description: The safety and tolerability of olaparib treatment in HER2-ve metastatic breast cancer patients in a real-word setting was evaluated.
arm group label: Olaparib
arm group type: Experimental
description: Olaparib 150mg tablets administered orally twice daily continuously
intervention type: Drug
intervention name: Olaparib
description: Patients will be administered olaparib orally, twice daily at 300 mg. Two (2) 150 mg olaparib tablets should be taken at the same time each morning and evening of every day, approximately 12 hours apart.
arm group label: Olaparib
criteria: 
gender: All
minimum age: 18 Years
maximum age: 130 Years
healthy volunteers: No
last name: Karen Gelmon, MD, FRCPC
role: Principal Investigator
affiliation: BritishColumbiaCancerAgency, 600W.10th Ave,Vancouver,Canada.
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facility: 
facility: 
facility: 
country: Bulgaria
country: Canada
country: France
country: Germany
country: Hungary
country: Italy
country: Japan
country: Korea, Republic of
country: Poland
country: Russian Federation
country: Spain
country: Taiwan
country: Turkey
country: United Kingdom
country: United States
country: Australia
country: China
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description: CSP_redacted
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description: SAP_redacted
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description: Related Info
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Olaparib
sharing ipd: Yes
ipd description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd access criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd url: https://astrazenecagroup-dt.pharmacm.com/DT/Home
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 