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    Clinical Trial Results:
    An Open Label, Single Arm, Multicentre Study to Assess the Clinical Effectiveness and Safety of Lynparza (Olaparib) Capsules Maintenance Monotherapy in Platinum Sensitive Relapsed Somatic or Germline BRCA Mutated Ovarian Cancer Patients who are in Complete or Partial Response Following Platinum based Chemotherapy (ORZORA)

    Summary
    EudraCT number
    		 2015-000734-30
    Trial protocol
    		 GB   CZ   ES   HU   BG   PL  
    Global end of trial date
    17 Dec 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 Oct 2022
    First version publication date
    11 Oct 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D0816C00012
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02476968
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca
    Sponsor organisation address
    Karlebyhusentren, B674 Astraallen, Södertälje, Sweden, 151 85
    Public contact
    Global Clinical Lead, AstraZeneca, +1 877-240-9479, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca, +1 877-240-9479, information.center@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    25 Jun 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Dec 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the real-world clinical effectiveness of olaparib maintenance monotherapy by Investigator-assessed progression-free survival (PFS) according to modified Response Evaluation Criteria In Solid Tumours (RECIST) v1.1 in patients with somatic breast cancer susceptibility gene mutated (sBRCAm) ovarian cancer. To assess the real-world clinical effectiveness of olaparib maintenance monotherapy by Investigator-assessed PFS according to RECIST v1.1 in patients with BRCAm ovarian cancer.
    Protection of trial subjects
    This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with International Council for Harmonisation/Good Clinical Practice, applicable regulatory requirements and the AstraZeneca policy on Bioethics.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 Sep 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 32 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Bulgaria: 34
    Country: Number of subjects enrolled
    Canada: 13
    Country: Number of subjects enrolled
    Czechia: 23
    Country: Number of subjects enrolled
    Spain: 28
    Country: Number of subjects enrolled
    United Kingdom: 35
    Country: Number of subjects enrolled
    Hungary: 17
    Country: Number of subjects enrolled
    Italy: 17
    Country: Number of subjects enrolled
    Poland: 14
    Worldwide total number of subjects
    181
    EEA total number of subjects
    133
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    108
    From 65 to 84 years
    73
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was conducted in patients with platinum sensitive relapsed high grade epithelial ovarian (including fallopian tube or primary peritoneal) cancer, who were in complete or partial response to platinum-based chemotherapy.

    Pre-assignment
    Screening details
    		 181 patients enrolled and assigned to olaparib: 145 with breast cancer susceptibility gene mutation (BRCAm) status (87 with germline mutations [gBRCAm], 55 with somatic mutations [sBRCAm] and 3 with undetermined BRCAm status), 33 with BRCA-independent homologous recombination repair mutation (HRRm^) status, and 3 enrolled in error (unassigned).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Overall BRCAm
    Arm description
    		 Patients received olaparib capsules orally 400 milligrams (mg) twice daily. Patients in this cohort had BRCAm status, comprising of those with sBRCAm or gBRCAm disease, as well as any patients where the germline or somatic BRCA mutation status was not determined.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Olaparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Patients were administered eight 50 mg olaparib capsules (i.e, 400 mg), which were to be taken twice daily at the same time each day approximately 12 hours apart with approximately 240 milliliter (mL) of water.

    Arm title
    		 HRRm^
    Arm description
    		 Patients received olaparib capsules orally 400 mg twice daily. Patients in this exploratory cohort had a qualifying mutation in any of the 13 genes involved in the HRR pathway (excluding BRCA1 and BRCA2) (i.e, BRCA-independent HRRm^).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Olaparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Patients were administered eight 50 mg olaparib capsules (i.e, 400 mg), which were to be taken twice daily at the same time each day approximately 12 hours apart with approximately 240 mL of water.

    Arm title
    		 Unassigned (not BRCAm, not HRRm^)
    Arm description
    		 Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort were not classified as being a part of either the BRCAm group or the HRRm^ group and were enrolled in error.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Olaparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Patients were administered eight 50 mg olaparib capsules (i.e, 400 mg), which were to be taken twice daily at the same time each day approximately 12 hours apart with approximately 240 mL of water.

    Number of subjects in period 1
    		Overall BRCAm HRRm^ Unassigned (not BRCAm, not HRRm^)
    Started
    145
    33
    3
    Received treatment
    143
    32
    2
    Completed
    50
    15
    0
    Not completed
    95
    18
    3
         Patient decision
    37
    8
    -
         Eligibility criteria not fulfilled
    -
    -
    1
         Death
    48
    8
    1
         Unspecified
    -
    2
    -
         Lost to follow-up
    10
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall BRCAm
    Reporting group description
    		 Patients received olaparib capsules orally 400 milligrams (mg) twice daily. Patients in this cohort had BRCAm status, comprising of those with sBRCAm or gBRCAm disease, as well as any patients where the germline or somatic BRCA mutation status was not determined.

    Reporting group title
    HRRm^
    Reporting group description
    		 Patients received olaparib capsules orally 400 mg twice daily. Patients in this exploratory cohort had a qualifying mutation in any of the 13 genes involved in the HRR pathway (excluding BRCA1 and BRCA2) (i.e, BRCA-independent HRRm^).

    Reporting group title
    Unassigned (not BRCAm, not HRRm^)
    Reporting group description
    		 Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort were not classified as being a part of either the BRCAm group or the HRRm^ group and were enrolled in error.

    Reporting group values
    		 Overall BRCAm HRRm^ Unassigned (not BRCAm, not HRRm^) Total
    Number of subjects
    		 145 33 3 181
    Age Categorical
    Units: Participants
        <35 years
    		 0 0 0 0
        ≥35 to <50 years
    		 29 3 0 32
        ≥50 to <65 years
    		 61 13 2 76
        ≥65 to <80 years
    		 54 17 1 72
        ≥80 years
    		 1 0 0 1
    Sex: Female, Male
    Units: Participants
        Female
    		 145 33 3 181
        Male
    		 0 0 0 0
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 142 31 3 176
        Asian
    		 2 1 0 3
        Other
    		 1 0 0 1
        Unknown or Not Reported
    		 0 1 0 1
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 3 1 0 4
        Not Hispanic or Latino
    		 142 31 3 176
        Unknown or Not Reported
    		 0 1 0 1

    End points

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    End points reporting groups
    Reporting group title
    Overall BRCAm
    Reporting group description
    		 Patients received olaparib capsules orally 400 milligrams (mg) twice daily. Patients in this cohort had BRCAm status, comprising of those with sBRCAm or gBRCAm disease, as well as any patients where the germline or somatic BRCA mutation status was not determined.

    Reporting group title
    HRRm^
    Reporting group description
    		 Patients received olaparib capsules orally 400 mg twice daily. Patients in this exploratory cohort had a qualifying mutation in any of the 13 genes involved in the HRR pathway (excluding BRCA1 and BRCA2) (i.e, BRCA-independent HRRm^).

    Reporting group title
    Unassigned (not BRCAm, not HRRm^)
    Reporting group description
    		 Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort were not classified as being a part of either the BRCAm group or the HRRm^ group and were enrolled in error.

    Subject analysis set title
    sBRCAm
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had sBRCAm disease (i.e. confirmed somatic mutation).

    Primary: Progression-Free Survival (PFS)

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    End point title
    		 Progression-Free Survival (PFS) [1] [2]
    End point description
    The PFS was defined as the time from the date of enrolment until date of objective radiological disease progression (assessed by the Investigator via, RECIST version 1.1), or death (by any cause in absence of disease progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to disease progression. Objective progression was defined as at least a 20% increase in the sum of the diameters of the target lesions (compared to previous minimum sum) and an absolute increase of > 5 millimeters, or an overall non-target lesion assessment of progression or a new lesion. The data cut-off (DCO) for the primary analysis of the study occurred after approximately 60% maturity of PFS in the sBRCAm and all BRCAm patient populations. The FAS included all enrolled patients who were assigned olaparib. The primary endpoint results for PFS assessment included only BRCAm and sBRCAm patients.
    End point type
    Primary
    End point timeframe
    Tumour assessments at baseline then every 12 weeks relative to date of enrolment until RECIST 1.1-defined progression. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months).
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only participants treated in Overall BRCAm reporting group and sBRCAm subject analysis set were analyzed for the primary endpoint.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only participants treated in Overall BRCAm reporting group and sBRCAm subject analysis set were analyzed for the primary endpoint.
    End point values
    		 Overall BRCAm sBRCAm
    Number of subjects analysed
    145
    55
    Units: months
        median (confidence interval 95%)
    18.0 (14.3 to 22.1)
    16.6 (12.4 to 22.2)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS); Assessed at Primary Analysis

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    End point title
    		 Overall Survival (OS); Assessed at Primary Analysis [3]
    End point description
    The OS was defined as the time from the date of enrolment until death due to any cause regardless of whether the patient withdrew from therapy or received another anti-cancer therapy. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Pre-specified analysis of OS was performed at the time of primary analysis of PFS; a further analysis of OS was performed after approximately 60% maturity of OS in the sBRCAm and all BRCAm patient populations (and reported as a separate outcome measure). The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for OS assessment included only BRCAm and sBRCAm patients. 9999 indicates that the median and upper limit 95% confidence interval (CI) could not be calculated as it was not reached.
    End point type
    Secondary
    End point timeframe
    From baseline until death due to any cause. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months).
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only participants treated in Overall BRCAm reporting group and sBRCAm subject analysis set were analyzed for the primary endpoint.
    End point values
    		 Overall BRCAm sBRCAm
    Number of subjects analysed
    145
    55
    Units: months
        median (confidence interval 95%)
    47.6 (36.1 to 9999)
    9999 (33.2 to 9999)
    No statistical analyses for this end point

    Secondary: Time to Second Progression (PFS2) or Death; Assessed at Primary Analysis

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    End point title
    		 Time to Second Progression (PFS2) or Death; Assessed at Primary Analysis [4]
    End point description
    The PFS2 was defined as the time from the date of enrolment to the earliest progression event subsequent to that used for the primary variable PFS or death (by any cause) in the absence of progression. Patients whose progression event for PFS was death had this counted as a progression event for PFS2 also. The date of second progression was recorded by the Investigator and defined according to local standard clinical practice and could involve any of the following: objective radiological, symptomatic, cancer antigen-125 (CA-125) progression or death. Pre-specified analysis of PFS2 was performed at the time of the primary analysis; a further analysis of PFS2 was performed at the final analysis (and reported as a separate outcome measure). The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for PFS2 assessment included only BRCAm and sBRCAm patients.
    End point type
    Secondary
    End point timeframe
    Tumour assessments (and blood samples for CA-125, if applicable) at baseline then every 12 weeks relative to date of enrolment until second progression. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months).
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only participants treated in Overall BRCAm reporting group and sBRCAm subject analysis set were analyzed for the primary endpoint.
    End point values
    		 Overall BRCAm sBRCAm
    Number of subjects analysed
    145
    55
    Units: months
        median (confidence interval 95%)
    30.9 (24.7 to 40.0)
    24.7 (21.8 to 36.1)
    No statistical analyses for this end point

    Secondary: Time to First Subsequent Therapy (Treatment) or Death (TFST); Assessed at Primary Analysis

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    End point title
    		 Time to First Subsequent Therapy (Treatment) or Death (TFST); Assessed at Primary Analysis [5]
    End point description
    To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of TFST. The TFST was defined as the time from the date of enrolment to the earlier of first subsequent anti-cancer therapy start date (excluding radiotherapy), or death date. Pre-specified analysis of TFST was performed at the time of the primary analysis; a further analysis of TFST was performed at the final analysis (and reported as a separate outcome measure). The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for TFST assessment included only BRCAm and sBRCAm patients. 9999 indicates that the upper limit 95% CI could not be calculated as it was not reached.
    End point type
    Secondary
    End point timeframe
    From enrolment to first subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months).
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only participants treated in Overall BRCAm reporting group and sBRCAm subject analysis set were analyzed for the primary endpoint.
    End point values
    		 Overall BRCAm sBRCAm
    Number of subjects analysed
    145
    55
    Units: months
        median (confidence interval 95%)
    37.6 (23.5 to 47.6)
    31.5 (19.5 to 9999)
    No statistical analyses for this end point

    Secondary: Time to Second Subsequent Therapy (Treatment) or Death (TSST); Assessed at Primary Analysis

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    End point title
    		 Time to Second Subsequent Therapy (Treatment) or Death (TSST); Assessed at Primary Analysis [6]
    End point description
    To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of TSST. The TSST was defined as the time from the date of enrolment to the earlier of the date of second subsequent anti-cancer therapy start date, or death date. Pre-specified analysis of TSST was performed at the time of the primary analysis; a further analysis of TSST was performed at the final analysis (and reported as a separate outcome measure). The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for TSST assessment included only BRCAm and sBRCAm patients. 9999 indicates that the median and upper limit 95% CI could not be calculated as they were not reached.
    End point type
    Secondary
    End point timeframe
    From enrolment to second subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months).
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only participants treated in Overall BRCAm reporting group and sBRCAm subject analysis set were analyzed for the primary endpoint.
    End point values
    		 Overall BRCAm sBRCAm
    Number of subjects analysed
    145
    55
    Units: months
        median (confidence interval 95%)
    47.6 (29.4 to 9999)
    9999 (24.7 to 9999)
    No statistical analyses for this end point

    Secondary: Time to Discontinuation of Treatment or Death (TDT)

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    End point title
    		 Time to Discontinuation of Treatment or Death (TDT) [7]
    End point description
    To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of TDT. The TDT was defined as the time from the date of enrolment to the earlier of the date of study treatment discontinuation or death. The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for TDT assessment included only BRCAm and sBRCAm patients.
    End point type
    Secondary
    End point timeframe
    From enrolment to study treatment discontinuation or death (up to maximum of 6 years).
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only participants treated in Overall BRCAm reporting group and sBRCAm subject analysis set were analyzed for the primary endpoint.
    End point values
    		 Overall BRCAm sBRCAm
    Number of subjects analysed
    145
    55
    Units: months
        median (confidence interval 95%)
    19.8 (14.3 to 22.9)
    19.0 (13.5 to 22.8)
    No statistical analyses for this end point

    Secondary: Change from Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time; Assessed at Primary Analysis

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    End point title
    		 Change from Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time; Assessed at Primary Analysis [8]
    End point description
    The Quality of Life (QoL) of patients with BRCAm and sBRCAm ovarian cancer was assessed by FACT-O TOI. The TOI score was derived from the sum of the scores of the 25 items included in the physical well-being (7 items), functional well-being (7 items), and additional concerns ovarian cancer subscale (11 items) of the FACT-O questionnaire version 4. The FACT-O TOI score ranges from 0-100, with a higher score indicating better QoL. A change (increase or decrease) in score of at least 10 points from baseline was defined as clinically meaningful. A positive change in score from baseline indicates an improvement. The FAS-FACT-O-TOI population included all enrolled patients who were assigned olaparib excluding patients who did not have FACT-O TOI score at baseline and patients who did not have any FACT-O TOI score post-baseline. The secondary endpoint results for FACT-O TOI assessment included only BRCAm and sBRCAm patients. Here, n= number of participants analysed in each analysis set.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 29 (Week 4), then every 12 weeks for 24 months or DCO (17 April 2020) for primary analysis, whichever came first. QoL questionnaires also collected at discontinuation of study treatment visit and 30 days post last dose.
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only participants treated in Overall BRCAm reporting group and sBRCAm subject analysis set were analyzed for the primary endpoint.
    End point values
    		 Overall BRCAm sBRCAm
    Number of subjects analysed
    131
    50
    Units: scores on a scale
    arithmetic mean (standard deviation)
        Week 4, n=126, 47
    -2.2 ( 9.82 )
    -1.9 ( 9.59 )
        Week 16, n=91, 31
    -1.3 ( 10.04 )
    -0.3 ( 10.85 )
        Week 28, n=82, 30
    1.2 ( 9.44 )
    3.2 ( 10.25 )
        Week 40, n=80, 28
    1.6 ( 10.72 )
    4.1 ( 10.48 )
        Week 52, n=70, 24
    3.2 ( 9.03 )
    4.9 ( 7.84 )
        Week 64, n=60, 23
    1.8 ( 9.88 )
    0.8 ( 9.72 )
        Week 76, n=57, 20
    1.4 ( 9.27 )
    0.3 ( 9.83 )
        Week 88, n=46, 15
    2.0 ( 9.97 )
    1.5 ( 10.86 )
        Week 100, n=34, 11
    -0.2 ( 9.41 )
    -3.5 ( 7.54 )
        Discontinuation of olaparib visit,n=36,16
    -4.7 ( 13.00 )
    -7.4 ( 15.53 )
        30 days post discontinuation,n=52,24
    -8.0 ( 13.45 )
    -4.3 ( 13.36 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time; Assessed at Primary Analysis

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    End point title
    		 Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time; Assessed at Primary Analysis [9]
    End point description
    To assess the QoL of patients with BRCAm and sBRCAm ovarian cancer by evaluation of FACIT-F. The FACIT-F is a 13-item questionnaire to assess patients’ fatigue experience and its impact on their daily lives over the past 7 days. The FACIT-F total score ranges from 0-52, with a higher score indicating a lower level of fatigue (and better QoL). Changes in scores of ≥3 points were defined to be clinically meaningful. A positive change in score from baseline indicates an improvement. The FAS-FACIT-F population included all enrolled patients who were assigned olaparib excluding patients who did not have FACIT-F total score at baseline and patients who did not have any FACIT-F total score post-baseline. The secondary endpoint results for FACIT-F assessment included only BRCAm and sBRCAm patients. Here, n= number of patients analysed at specific timepoint.
    End point type
    Secondary
    End point timeframe
    At baseline, Day 29 (Week 4), then every 12 weeks for 24 months or DCO (17 April 2020) for primary analysis, whichever came first. QoL questionnaires also collected at discontinuation of study treatment visit and 30 days post last dose.
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only participants treated in Overall BRCAm reporting group and sBRCAm subject analysis set were analyzed for the primary endpoint.
    End point values
    		 Overall BRCAm sBRCAm
    Number of subjects analysed
    136
    53
    Units: scores on a scale
    arithmetic mean (standard deviation)
        Week 4, n=130, 48
    -2.9 ( 8.21 )
    -2.9 ( 7.58 )
        Week 16, n=95, 34
    -2.5 ( 7.54 )
    -2.7 ( 9.26 )
        Week 28, n= 83, 31
    -1.2 ( 7.95 )
    -0.6 ( 7.25 )
        Week 40, n= 83, 31
    -0.3 ( 7.91 )
    0.9 ( 7.02 )
        Week 52, n= 76, 29
    0.6 ( 7.43 )
    1.3 ( 7.25 )
        Week 64, n= 65, 25
    0.8 ( 7.26 )
    0.5 ( 8.47 )
        Week 76, n= 58, 21
    -0.3 ( 8.57 )
    -1.1 ( 8.74 )
        Week 88, n= 46, 14
    0.3 ( 8.45 )
    -0.9 ( 5.81 )
        Week 100, n= 34, 11
    -0.4 ( 8.59 )
    -1.3 ( 8.75 )
        Discontinuation of olaparib visit,n=37,16
    -2.3 ( 9.01 )
    -2.7 ( 9.32 )
        30 days post discontinuation,n=53,24
    -5.2 ( 11.16 )
    -3.8 ( 9.65 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time; Assessed at Primary Analysis

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    End point title
    		 Change from Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time; Assessed at Primary Analysis [10]
    End point description
    The FLIE captures the impact of nausea and vomiting on patient’s QoL. The FLIE consists of 18 items (9 nausea-specific and 9 vomiting-specific items), rated from 1 to 7. Two domain scores and a total score are derived; the total score ranges 18-126 and a higher score indicates a lower impact (and better QoL). A positive change in score from baseline indicates an improvement. The FAS-FLIE population included all enrolled patients who were assigned olaparib excluding patients who did not have FLIE total score at baseline and patients who did not have any FLIE total score post-baseline. The secondary endpoint results for FLIE assessment included only BRCAm and sBRCAm patients. Here, n= number of patients analysed at specific timepoint.
    End point type
    Secondary
    End point timeframe
    At baseline, weekly until Day 29 (Week 4), then every 12 weeks for 24 months or DCO (17 April 2020) for primary analysis, whichever came first. FLIE questionnaires also collected at discontinuation of study treatment visit and 30 days post last dose.
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only participants treated in Overall BRCAm reporting group and sBRCAm subject analysis set were analyzed for the primary endpoint.
    End point values
    		 Overall BRCAm sBRCAm
    Number of subjects analysed
    114
    46
    Units: scores on a scale
    arithmetic mean (standard deviation)
        Week 1, n= 105, 42
    -6.1 ( 18.62 )
    -1.6 ( 18.28 )
        Week 2, n= 101, 39
    -4.5 ( 18.40 )
    -2.6 ( 15.97 )
        Week 3, n= 102, 40
    -4.1 ( 14.57 )
    -3.9 ( 13.23 )
        Week 4, n= 103, 39
    -4.8 ( 18.48 )
    -5.4 ( 19.92 )
        Week 16, n= 80, 29
    -2.3 ( 11.50 )
    -6.3 ( 11.00 )
        Week 28, n= 73, 28
    -1.6 ( 13.87 )
    -3.0 ( 7.94 )
        Week 40, n= 72, 28
    -0.1 ( 14.07 )
    -3.2 ( 14.56 )
        Week 52, n= 64, 26
    0.9 ( 14.41 )
    -1.9 ( 11.64 )
        Week 64, n= 54, 23
    -0.2 ( 15.93 )
    -1.0 ( 20.77 )
        Week 76, n= 49, 19
    0.9 ( 14.14 )
    0.6 ( 6.60 )
        Week 88, n= 42, 14
    2.2 ( 10.04 )
    -1.3 ( 9.29 )
        Week 100, n= 32, 11
    0.4 ( 10.37 )
    0.1 ( 13.19 )
        Discontinuation of olaparib visit,n=28,12
    -0.7 ( 20.17 )
    -8.8 ( 21.57 )
        30 days post discontinuation,n=39,18
    -5.2 ( 17.02 )
    -5.6 ( 15.69 )
    No statistical analyses for this end point

    Secondary: OS; Assessed at Final Analysis

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    End point title
    		 OS; Assessed at Final Analysis [11]
    End point description
    To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of OS. The OS was defined as the time from the date of enrolment until death due to any cause regardless of whether the patient withdrew from therapy or received another anti-cancer therapy. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for OS assessment included only BRCAm and sBRCAm patients. 9999 indicates that the upper limit 95% CI could not be calculated as it was not reached.
    End point type
    Secondary
    End point timeframe
    From baseline until death due to any cause (up to maximum of 6 years).
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only participants treated in Overall BRCAm reporting group and sBRCAm subject analysis set were analyzed for the primary endpoint.
    End point values
    		 Overall BRCAm sBRCAm
    Number of subjects analysed
    145
    55
    Units: months
        median (confidence interval 95%)
    46.8 (37.9 to 54.4)
    43.2 (31.7 to 9999)
    No statistical analyses for this end point

    Secondary: PFS2 or Death; Assessed at Final Analysis

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    End point title
    		 PFS2 or Death; Assessed at Final Analysis [12]
    End point description
    To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of PFS2. The PFS2 was defined as the time from the date of enrolment to the earliest progression event subsequent to that used for the primary variable PFS or death (by any cause) in the absence of progression. Patients whose progression event for PFS was death had this counted as a progression event for PFS2 also. The date of second progression was recorded by the Investigator and defined according to local standard clinical practice and could involve any of the following: objective radiological, symptomatic, CA-125 progression or death. The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for PFS2 assessment included only BRCAm and sBRCAm patients.
    End point type
    Secondary
    End point timeframe
    Tumour assessments (and blood samples for CA-125, if applicable) at baseline then every 12 weeks relative to date of enrolment until second progression (up to maximum of 6 years).
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only participants treated in Overall BRCAm reporting group and sBRCAm subject analysis set were analyzed for the primary endpoint.
    End point values
    		 Overall BRCAm sBRCAm
    Number of subjects analysed
    145
    55
    Units: months
        median (confidence interval 95%)
    34.0 (29.3 to 44.2)
    29.3 (23.7 to 44.2)
    No statistical analyses for this end point

    Secondary: TFST; Assessed at Final Analysis

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    End point title
    		 TFST; Assessed at Final Analysis [13]
    End point description
    To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of TFST. The TFST was defined as the time from the date of enrolment to the earlier of first subsequent anti-cancer therapy start date (excluding radiotherapy), or death date. The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for TFST assessment included only BRCAm and sBRCAm patients. 9999 indicates that the upper limit 95% CI could not be calculated as it was not reached.
    End point type
    Secondary
    End point timeframe
    From enrolment to first subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation (up to maximum of 6 years).
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only participants treated in Overall BRCAm reporting group and sBRCAm subject analysis set were analyzed for the primary endpoint.
    End point values
    		 Overall BRCAm sBRCAm
    Number of subjects analysed
    145
    55
    Units: months
        median (confidence interval 95%)
    32.1 (25.8 to 40.0)
    31.7 (18.0 to 9999)
    No statistical analyses for this end point

    Secondary: TSST; Assessed at Final Analysis

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    End point title
    		 TSST; Assessed at Final Analysis [14]
    End point description
    To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of TSST. The TSST was defined as the time from the date of enrolment to the earlier of the date of second subsequent anti-cancer therapy start date, or death date. The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for TSST assessment included only BRCAm and sBRCAm patients. 9999 indicates that the upper limit 95% CI could not be calculated as it was not reached.
    End point type
    Secondary
    End point timeframe
    From enrolment to second subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation (up to maximum 6 years).
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only participants treated in Overall BRCAm reporting group and sBRCAm subject analysis set were analyzed for the primary endpoint.
    End point values
    		 Overall BRCAm sBRCAm
    Number of subjects analysed
    145
    55
    Units: months
        median (confidence interval 95%)
    38.4 (31.5 to 9999)
    32.1 (25.8 to 44.7)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of olaparib up to and including 30 days following the date of discontinuation of olaparib. Maximum timeframe of approximately 6 years.
    Adverse event reporting additional description
    Adverse events are reported for the safety analysis set which included all patients who received at least one dose of olaparib. Total number of deaths was determined for patients in the FAS (enrolled and assigned olaparib).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    gBRCAm
    Reporting group description
    		 Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had gBRCAm disease (i.e, confirmed germline mutation).

    Reporting group title
    sBRCAm
    Reporting group description
    		 Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had sBRCAm disease (i.e, confirmed somatic mutation).

    Reporting group title
    Overall BRCAm
    Reporting group description
    		 Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had BRCAm status, comprising of those with sBRCAm or gBRCAm disease, as well as any patients where the germline or somatic BRCA mutation status was not determined.

    Reporting group title
    HRRm^
    Reporting group description
    		 Patients received olaparib capsules orally 400 mg twice daily. Patients in this exploratory cohort had a qualifying mutation in any of the 13 genes involved in the HRR pathway (excluding BRCA1 and BRCA2) (i.e, BRCA-independent HRRm^).

    Reporting group title
    Unassigned (not BRCAm, not HRRm^)
    Reporting group description
    		 Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort were not classified as being a part of either the BRCAm group or the HRRm^ group and were enrolled in error.

    Serious adverse events
    		 gBRCAm sBRCAm Overall BRCAm HRRm^ Unassigned (not BRCAm, not HRRm^)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    27 / 87 (31.03%)
    13 / 55 (23.64%)
    40 / 143 (27.97%)
    7 / 32 (21.88%)
    1 / 2 (50.00%)
         number of deaths (all causes)
    40
    28
    68
    14
    2
         number of deaths resulting from adverse events
    4
    0
    4
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    2 / 87 (2.30%)
    0 / 55 (0.00%)
    2 / 143 (1.40%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    2 / 2
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    Burkitt's lymphoma
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 55 (0.00%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 55 (0.00%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 55 (1.82%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    1 / 87 (1.15%)
    1 / 55 (1.82%)
    2 / 143 (1.40%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-Hodgkin's lymphoma
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 55 (0.00%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 55 (1.82%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 55 (1.82%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 55 (0.00%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Immune system disorders
    Contrast media allergy
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 55 (1.82%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 55 (0.00%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 55 (0.00%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 55 (0.00%)
    0 / 143 (0.00%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    3 / 87 (3.45%)
    0 / 55 (0.00%)
    3 / 143 (2.10%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Platelet count decreased
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 55 (1.82%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femoral neck fracture
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 55 (1.82%)
    1 / 143 (0.70%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 55 (0.00%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Angina unstable
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 55 (0.00%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 55 (1.82%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 55 (0.00%)
    0 / 143 (0.00%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 55 (1.82%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Transient ischaemic attack
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 55 (0.00%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    7 / 87 (8.05%)
    5 / 55 (9.09%)
    12 / 143 (8.39%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    9 / 10
    5 / 6
    14 / 16
    10 / 10
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 55 (0.00%)
    0 / 143 (0.00%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 55 (0.00%)
    0 / 143 (0.00%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Glaucoma
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 55 (0.00%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 55 (0.00%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mesenteric vein thrombosis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 55 (0.00%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 55 (1.82%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    1 / 2 (50.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 55 (1.82%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 55 (0.00%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary colic
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 55 (1.82%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Colonic abscess
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 55 (1.82%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 55 (0.00%)
    0 / 143 (0.00%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 55 (0.00%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 55 (0.00%)
    1 / 143 (0.70%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    3 / 87 (3.45%)
    0 / 55 (0.00%)
    3 / 143 (2.10%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 gBRCAm sBRCAm Overall BRCAm HRRm^ Unassigned (not BRCAm, not HRRm^)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    79 / 87 (90.80%)
    51 / 55 (92.73%)
    131 / 143 (91.61%)
    29 / 32 (90.63%)
    1 / 2 (50.00%)
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 55 (0.00%)
    1 / 143 (0.70%)
    2 / 32 (6.25%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    1
    2
    0
    Hypertension
         subjects affected / exposed
    3 / 87 (3.45%)
    3 / 55 (5.45%)
    6 / 143 (4.20%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences all number
    3
    3
    6
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    13 / 87 (14.94%)
    11 / 55 (20.00%)
    24 / 143 (16.78%)
    2 / 32 (6.25%)
    0 / 2 (0.00%)
         occurrences all number
    19
    14
    33
    2
    0
    Fatigue
         subjects affected / exposed
    38 / 87 (43.68%)
    22 / 55 (40.00%)
    60 / 143 (41.96%)
    15 / 32 (46.88%)
    1 / 2 (50.00%)
         occurrences all number
    46
    25
    71
    18
    1
    Influenza like illness
         subjects affected / exposed
    7 / 87 (8.05%)
    2 / 55 (3.64%)
    9 / 143 (6.29%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    8
    2
    10
    0
    0
    Mucosal inflammation
         subjects affected / exposed
    1 / 87 (1.15%)
    3 / 55 (5.45%)
    4 / 143 (2.80%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences all number
    1
    3
    4
    1
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 87 (0.00%)
    6 / 55 (10.91%)
    6 / 143 (4.20%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences all number
    0
    8
    8
    1
    0
    Peripheral swelling
         subjects affected / exposed
    5 / 87 (5.75%)
    2 / 55 (3.64%)
    7 / 143 (4.90%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    5
    3
    8
    0
    0
    Pyrexia
         subjects affected / exposed
    6 / 87 (6.90%)
    2 / 55 (3.64%)
    8 / 143 (5.59%)
    2 / 32 (6.25%)
    0 / 2 (0.00%)
         occurrences all number
    9
    4
    13
    2
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    9 / 87 (10.34%)
    5 / 55 (9.09%)
    14 / 143 (9.79%)
    6 / 32 (18.75%)
    0 / 2 (0.00%)
         occurrences all number
    12
    5
    17
    6
    0
    Dyspnoea
         subjects affected / exposed
    10 / 87 (11.49%)
    4 / 55 (7.27%)
    14 / 143 (9.79%)
    6 / 32 (18.75%)
    0 / 2 (0.00%)
         occurrences all number
    26
    8
    34
    7
    0
    Oropharyngeal pain
         subjects affected / exposed
    3 / 87 (3.45%)
    1 / 55 (1.82%)
    4 / 143 (2.80%)
    2 / 32 (6.25%)
    0 / 2 (0.00%)
         occurrences all number
    5
    1
    6
    2
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    4 / 87 (4.60%)
    3 / 55 (5.45%)
    7 / 143 (4.90%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    4
    3
    7
    0
    0
    Depression
         subjects affected / exposed
    4 / 87 (4.60%)
    3 / 55 (5.45%)
    7 / 143 (4.90%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences all number
    4
    3
    7
    1
    0
    Insomnia
         subjects affected / exposed
    7 / 87 (8.05%)
    4 / 55 (7.27%)
    11 / 143 (7.69%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences all number
    7
    4
    11
    1
    0
    Irritability
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 55 (0.00%)
    0 / 143 (0.00%)
    0 / 32 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    0
    0
    0
    1
    Personality change
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 55 (0.00%)
    0 / 143 (0.00%)
    0 / 32 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    0
    0
    0
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    7 / 87 (8.05%)
    1 / 55 (1.82%)
    8 / 143 (5.59%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences all number
    11
    1
    12
    2
    0
    Blood creatinine increased
         subjects affected / exposed
    8 / 87 (9.20%)
    3 / 55 (5.45%)
    11 / 143 (7.69%)
    4 / 32 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    21
    3
    24
    6
    0
    Glomerular filtration rate decreased
         subjects affected / exposed
    2 / 87 (2.30%)
    3 / 55 (5.45%)
    5 / 143 (3.50%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    5
    7
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    5 / 87 (5.75%)
    2 / 55 (3.64%)
    7 / 143 (4.90%)
    1 / 32 (3.13%)
    1 / 2 (50.00%)
         occurrences all number
    8
    3
    11
    1
    1
    Platelet count decreased
         subjects affected / exposed
    5 / 87 (5.75%)
    1 / 55 (1.82%)
    6 / 143 (4.20%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences all number
    6
    1
    7
    2
    0
    White blood cell count decreased
         subjects affected / exposed
    5 / 87 (5.75%)
    2 / 55 (3.64%)
    7 / 143 (4.90%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences all number
    14
    7
    21
    1
    0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 87 (1.15%)
    1 / 55 (1.82%)
    2 / 143 (1.40%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    3
    5
    0
    0
    Injury, poisoning and procedural complications
    Foot fracture
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 55 (0.00%)
    0 / 143 (0.00%)
    0 / 32 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    0
    0
    0
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    13 / 87 (14.94%)
    2 / 55 (3.64%)
    15 / 143 (10.49%)
    5 / 32 (15.63%)
    0 / 2 (0.00%)
         occurrences all number
    21
    3
    24
    6
    0
    Dysgeusia
         subjects affected / exposed
    8 / 87 (9.20%)
    3 / 55 (5.45%)
    11 / 143 (7.69%)
    4 / 32 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    10
    3
    13
    4
    0
    Headache
         subjects affected / exposed
    11 / 87 (12.64%)
    3 / 55 (5.45%)
    14 / 143 (9.79%)
    6 / 32 (18.75%)
    0 / 2 (0.00%)
         occurrences all number
    16
    11
    27
    8
    0
    Taste disorder
         subjects affected / exposed
    0 / 87 (0.00%)
    0 / 55 (0.00%)
    0 / 143 (0.00%)
    0 / 32 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    0
    0
    0
    1
    Peripheral sensory neuropathy
         subjects affected / exposed
    2 / 87 (2.30%)
    2 / 55 (3.64%)
    4 / 143 (2.80%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    4
    6
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    38 / 87 (43.68%)
    20 / 55 (36.36%)
    58 / 143 (40.56%)
    11 / 32 (34.38%)
    1 / 2 (50.00%)
         occurrences all number
    56
    32
    88
    16
    1
    Leukopenia
         subjects affected / exposed
    6 / 87 (6.90%)
    2 / 55 (3.64%)
    8 / 143 (5.59%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    6
    2
    8
    0
    0
    Neutropenia
         subjects affected / exposed
    12 / 87 (13.79%)
    4 / 55 (7.27%)
    16 / 143 (11.19%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences all number
    16
    10
    26
    1
    0
    Thrombocytopenia
         subjects affected / exposed
    5 / 87 (5.75%)
    6 / 55 (10.91%)
    11 / 143 (7.69%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences all number
    5
    7
    12
    4
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    6 / 87 (6.90%)
    2 / 55 (3.64%)
    8 / 143 (5.59%)
    3 / 32 (9.38%)
    0 / 2 (0.00%)
         occurrences all number
    7
    2
    9
    3
    0
    Abdominal pain
         subjects affected / exposed
    11 / 87 (12.64%)
    12 / 55 (21.82%)
    23 / 143 (16.08%)
    8 / 32 (25.00%)
    0 / 2 (0.00%)
         occurrences all number
    11
    20
    31
    9
    0
    Abdominal pain lower
         subjects affected / exposed
    3 / 87 (3.45%)
    0 / 55 (0.00%)
    3 / 143 (2.10%)
    3 / 32 (9.38%)
    0 / 2 (0.00%)
         occurrences all number
    4
    0
    4
    3
    0
    Abdominal pain upper
         subjects affected / exposed
    9 / 87 (10.34%)
    4 / 55 (7.27%)
    13 / 143 (9.09%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    13
    6
    19
    0
    0
    Constipation
         subjects affected / exposed
    5 / 87 (5.75%)
    8 / 55 (14.55%)
    13 / 143 (9.09%)
    5 / 32 (15.63%)
    0 / 2 (0.00%)
         occurrences all number
    6
    9
    15
    5
    0
    Diarrhoea
         subjects affected / exposed
    15 / 87 (17.24%)
    9 / 55 (16.36%)
    24 / 143 (16.78%)
    8 / 32 (25.00%)
    0 / 2 (0.00%)
         occurrences all number
    16
    11
    27
    9
    0
    Dyspepsia
         subjects affected / exposed
    14 / 87 (16.09%)
    8 / 55 (14.55%)
    23 / 143 (16.08%)
    5 / 32 (15.63%)
    0 / 2 (0.00%)
         occurrences all number
    27
    10
    38
    5
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    3 / 87 (3.45%)
    0 / 55 (0.00%)
    3 / 143 (2.10%)
    2 / 32 (6.25%)
    1 / 2 (50.00%)
         occurrences all number
    5
    0
    5
    2
    1
    Nausea
         subjects affected / exposed
    49 / 87 (56.32%)
    28 / 55 (50.91%)
    78 / 143 (54.55%)
    19 / 32 (59.38%)
    0 / 2 (0.00%)
         occurrences all number
    86
    36
    123
    30
    0
    Vomiting
         subjects affected / exposed
    24 / 87 (27.59%)
    15 / 55 (27.27%)
    39 / 143 (27.27%)
    10 / 32 (31.25%)
    1 / 2 (50.00%)
         occurrences all number
    41
    28
    69
    25
    1
    Haemorrhoids
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 55 (0.00%)
    1 / 143 (0.70%)
    2 / 32 (6.25%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    2
    2
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    7 / 87 (8.05%)
    4 / 55 (7.27%)
    11 / 143 (7.69%)
    2 / 32 (6.25%)
    0 / 2 (0.00%)
         occurrences all number
    9
    4
    13
    2
    0
    Pruritus
         subjects affected / exposed
    4 / 87 (4.60%)
    3 / 55 (5.45%)
    7 / 143 (4.90%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences all number
    5
    3
    8
    1
    0
    Rash
         subjects affected / exposed
    3 / 87 (3.45%)
    3 / 55 (5.45%)
    6 / 143 (4.20%)
    3 / 32 (9.38%)
    0 / 2 (0.00%)
         occurrences all number
    3
    3
    6
    3
    0
    Renal and urinary disorders
    Pollakiuria
         subjects affected / exposed
    3 / 87 (3.45%)
    2 / 55 (3.64%)
    5 / 143 (3.50%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences all number
    3
    2
    5
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    11 / 87 (12.64%)
    6 / 55 (10.91%)
    17 / 143 (11.89%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    15
    8
    23
    0
    0
    Back pain
         subjects affected / exposed
    7 / 87 (8.05%)
    4 / 55 (7.27%)
    11 / 143 (7.69%)
    3 / 32 (9.38%)
    0 / 2 (0.00%)
         occurrences all number
    11
    4
    15
    3
    0
    Muscle spasms
         subjects affected / exposed
    0 / 87 (0.00%)
    1 / 55 (1.82%)
    1 / 143 (0.70%)
    2 / 32 (6.25%)
    0 / 2 (0.00%)
         occurrences all number
    0
    2
    2
    2
    0
    Musculoskeletal pain
         subjects affected / exposed
    4 / 87 (4.60%)
    5 / 55 (9.09%)
    9 / 143 (6.29%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    4
    6
    10
    0
    0
    Myalgia
         subjects affected / exposed
    4 / 87 (4.60%)
    1 / 55 (1.82%)
    5 / 143 (3.50%)
    2 / 32 (6.25%)
    0 / 2 (0.00%)
         occurrences all number
    5
    1
    6
    2
    0
    Pain in extremity
         subjects affected / exposed
    4 / 87 (4.60%)
    2 / 55 (3.64%)
    6 / 143 (4.20%)
    3 / 32 (9.38%)
    0 / 2 (0.00%)
         occurrences all number
    7
    2
    9
    4
    0
    Infections and infestations
    Influenza
         subjects affected / exposed
    7 / 87 (8.05%)
    0 / 55 (0.00%)
    7 / 143 (4.90%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    13
    0
    13
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    9 / 87 (10.34%)
    3 / 55 (5.45%)
    12 / 143 (8.39%)
    2 / 32 (6.25%)
    0 / 2 (0.00%)
         occurrences all number
    12
    4
    16
    2
    0
    Oral candidiasis
         subjects affected / exposed
    1 / 87 (1.15%)
    0 / 55 (0.00%)
    1 / 143 (0.70%)
    2 / 32 (6.25%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    1
    2
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 87 (0.00%)
    3 / 55 (5.45%)
    3 / 143 (2.10%)
    2 / 32 (6.25%)
    0 / 2 (0.00%)
         occurrences all number
    0
    3
    3
    2
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 87 (2.30%)
    6 / 55 (10.91%)
    8 / 143 (5.59%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences all number
    3
    6
    9
    4
    0
    Urinary tract infection
         subjects affected / exposed
    6 / 87 (6.90%)
    6 / 55 (10.91%)
    12 / 143 (8.39%)
    4 / 32 (12.50%)
    0 / 2 (0.00%)
         occurrences all number
    10
    13
    23
    6
    0
    Bronchitis
         subjects affected / exposed
    5 / 87 (5.75%)
    1 / 55 (1.82%)
    6 / 143 (4.20%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    6
    1
    7
    0
    0
    Herpes zoster
         subjects affected / exposed
    3 / 87 (3.45%)
    0 / 55 (0.00%)
    3 / 143 (2.10%)
    1 / 32 (3.13%)
    0 / 2 (0.00%)
         occurrences all number
    3
    0
    3
    2
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    10 / 87 (11.49%)
    7 / 55 (12.73%)
    17 / 143 (11.89%)
    5 / 32 (15.63%)
    0 / 2 (0.00%)
         occurrences all number
    10
    8
    18
    6
    0
    Hypomagnesaemia
         subjects affected / exposed
    6 / 87 (6.90%)
    2 / 55 (3.64%)
    8 / 143 (5.59%)
    2 / 32 (6.25%)
    0 / 2 (0.00%)
         occurrences all number
    20
    2
    22
    3
    0
    Vitamin D deficiency
         subjects affected / exposed
    2 / 87 (2.30%)
    3 / 55 (5.45%)
    5 / 143 (3.50%)
    0 / 32 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    3
    5
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 Dec 2015
    Editorial change to improve clarity on study conduct, maintain consistency of information across protocol sections in line with revised AZ standard guidance. Expected proportion of patient populations specified. Revision of enrolment/screening procedures. Protocol compliance in European Union specified. Mutation testing details specified. Study design and flow chart updated. Co-primary endpoints finalised and details for their assessment specified. Secondary endpoints finalised and details for their assessment specified. Safety and exploratory objectives specified. Enrolment and screening procedures updated. Exclusion/inclusion criteria updated. Text added to align with Investigator's Brochure. Details specified for follow-up visits after discontinuation. Details related to tumour breast cancer susceptibility gene mutation testing specified. Removal of haemorrhage from Adverse event of special interest (AESI) list. Details about radiological assessments specified. Details of tumour samples required during central BRCA testing and exploratory testing specified. Steps for determination of mutation status aligned with revised screening procedures. Details on consent withdrawal and sample traceability updated. Details of BRACAnalysis® revised. Details for AESI updated. Drug interactions updated. Expected PFS/death events revised. Variables specified in the analysis sets. Details added for the efficacy analysis set. Secondary outcome measures specified to align with primary outcome measures and further details added. Details specified further for questionnaires/scales. Details for primary and QoL variable analyses, and sensitivity analyses updated.
    30 Jul 2016
    New exploratory cohort added. New exploratory objective and related outcomes measures added. Inclusion criteria updated. Collection of samples updated in tables. Screening procedure for exploratory HRRm^ cohort updated and details specified for circulating tumour deoxyribonucleic acid (ctDNA) analysis. Section added to provide further details for ctDNA analysis. Details of sample collection for exploratory analysis and ctDNA analysis added. Definitions and details of analysis sets updated.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    All patients in the FAS (enrolled and assigned olaparib) were included in the baseline characteristics data. For 17 patients in the FAS, only year of birth was reported. Therefore, age at enrollment imputed using year of birth.
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