To assess the efficacy and safety of olaparib maintenance monotherapy in the treatment of ovarian cancer - ORZORA

Study identifier:D0816C00012

ClinicalTrials.gov identifier:NCT02476968

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

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).

Medical condition

BRCA or HRR+ Mutated Ovarian Cancer Patients

Phase

Phase 4

Healthy volunteers

Study drug

Olaparib

Sex

Female

Actual Enrollment

181

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 28 Sept 2015

Primary Completion Date: 17 Apr 2020

Study Completion Date: 17 Dec 2021

Study design

Allocation: Non-randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Other

Verification:

Verified 01 Aug 2022 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1. Provision of informed consent prior to any study specific procedures
2. Age 18 years or over
3. Documented germline or somatic mutation in BRCA1 or BRCA2 genes that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function) [Genetic counselling for patients with germline BRCA mutations should be performed according to local regulations]
Or
Tumour BRCAwt status and documented qualifying mutation in any of 13 genes
involved in the HRR pathway, excluding BRCA1 and BRCA2 (ATM, BARD1, BRIP1,CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D,and RAD54L), identified by the Lynparza HRR Assay in archival tumour tissue (i.e.,BRCA-independent HRRm)
4. Patients with platinum sensitive relapsed high grade epithelial ovarian cancers
(including primary peritoneal and/or fallopian tube cancer):
− Platinum sensitive disease is defined as disease progression ≥6 months after
completion of their last dose of platinum based chemotherapy
5. Patients should have received at least 2 previous lines of platinum containing therapy prior to enrolment:
− For the last chemotherapy course immediately prior to enrolment on the study,
patients must be, in the opinion of the investigator, in response (partial or
complete radiological response) and no evidence of a rising CA-125, following
completion of this chemotherapy course.
6. Patients must have normal organ and bone marrow function measured within 28 days of enrolment, as defined below:
− Haemoglobin ≥ 10.0 g/dL with no blood transfusions in the past 28 days
− Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
− Platelet count ≥ 100 x 109/L
7. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), Aspartate
aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase [SGOT]) /
Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase [SGPT]) ≤ 2.5 x institutional ULN unless liver metastases are present in which case they must be ≤ 5x ULN
8. Creatinine clearance > 50 ml/min (calculated)
9. Patients must be postmenopausal or have evidence of non-childbearing status for women of childbearing potential.
Postmenopausal is defined as any of the following:
• Amenorrhoea for 1 year or more following cessation of exogenous hormonal
treatments
• For women under 50 years old, luteinizing hormone (LH) and follicle
stimulating hormone (FSH) levels in the post-menopausal range
• Radiation-induced oophorectomy, with interval of 1 year or more since last
menses
• Chemotherapy-induced menopause, with interval of 1 year or more since last
menses
• Surgical sterilisation (bilateral oophorectomy or hysterectomy).

Exclusion Criteria

1. Patients previously diagnosed with gBRCAm disease
2. Participation in another clinical study with an investigational product during the most
recent chemotherapy course
3. Patients with a known hypersensitivity to olaparib or any of the excipients of the
product
4. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative
reasons) or major surgery within 3 weeks prior to olaparib treatment. Major surgery
within 3 weeks of starting study treatment and patients must have recovered from any
effects of any major surgery
5. Persistent toxicities Common Terminology Criteria for Adverse Event (CTCAE) grade 2 caused by previous cancer therapy, excluding alopecia
6. Patients with myelodysplastic syndrome/acute myeloid leukaemia
7. Immuno-compromised patients e.g., Human Immunodeficiency Virus (HIV) requiring treatment or active Hepatitis B or C
8. Patients with symptomatic uncontrolled brain metastases. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease (SD) for 28 days
9. Patients considered to be at a high medical risk due to a serious, uncontrolled medical disorder, systemic disease or active, uncontrolled infection
10. Currently pregnant (confirmed with a positive pregnancy test) or breastfeeding.

The study will recruit approximately 250 patients with sBRCAm disease or gBRCAm disease, with the aim to accrue a minimum of 50 patients with sBRCAm disease. Patients with an unknown germline BRCA mutated status or gBRCAwt disease or previously identified as having a BRCAm disease by a tumour test will be considered for screening and will undergo, upon informed consent signature, central tumor and blood testing to determine their BRCA mutation status. In addition to central BRCA testing, patients screened for the study with unknown BRCA status or with known gBRCAwt status, for whom an adequate archival tumour tissue sample is available, will be tested for qualifying HRR gene alterations. Patients confirmed to carry a deleterious or suspected deleterious BRCA-independent genetic alteration in any of 13 genes involved in the Homologous Recombination Repair (HRR) pathway (HRRm cohort) will be allowed into an additional exploratory cohort (HRRm cohort). It is expected that approximately 25 patients will be included in the HRRm cohort before the target number of 250 patients with BRCAm disease is reached. Patients will be assigned olaparib capsules orally 400 mg twice daily. They should initiate olaparib treatment within 8 weeks after their last dose of platinum-containing chemotherapy (last dose is the day of the last infusion) and will be assessed every 4 weeks whilst on treatment. All patients will have clinical and objective radiological tumour assessments according to modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines at baseline and every 12 weeks relative to date of enrolment, until objective radiological disease progression as determined by the investigator. Patients could continue to receive olaparib for as long as determined by the investigator, until objective radiological disease progression or as long as in the investigator’s opinion they are benefiting from treatment in relation to other clinical assessments and they do not meet any other discontinuation criteria. Once a patient has discontinued olaparib she will be managed as per local clinical practice but will remain in the study and data will be collected on subsequent treatments, progression, overall survival and safety. For exploratory analysis purposes, patients will be asked to provide consent to: 1. Optional tumour samples at baseline and at disease progression 2. An optional blood sample only for patients with a confirmed sBRCAm or HRRm disease

Location

Research Site

Napoli, Italy, 80131

Location

Research Site

MILANO, Italy, 20141

Location

Research Site

Toronto, Ontario, Canada, M5G 1X6

Location

Research Site

London, ON, Canada, N6A 4L6

Location

Research Site

Oxford, United Kingdom, OX3 7LJ

Location

Research Site

Cardiff, United Kingdom, CF14 2TL

Location

Research Site

Calgary, AB, Canada, T2N 4N2

Location

Research Site

Leeds, United Kingdom, LS9 7TF

Arms	Assigned Interventions
Other: Olaparib Open Label Drug	Drug: Olaparib Olaparib Capsule – 50 mg. Olaparib capsules will be packed in high-density polyethylene (HDPE) bottles with child-resistant closures. Each bottle will contain 120 capsules and 4 bottles will be dispensed for a 4 weekly visit, with a 2 day overage. Patients will be administered olaparib capsules orally at a dose of 400 mg twice daily. Eight 50 mg olaparib capsules should be taken at the same time each day approximately 12 hours apart with approximately 240 mL of water. Other Name: Lynparza

Arms

Assigned Interventions

Other: Olaparib
Open Label Drug

Drug: Olaparib
Olaparib Capsule – 50 mg. Olaparib capsules will be packed in high-density polyethylene (HDPE) bottles with child-resistant closures. Each bottle will contain 120 capsules and 4 bottles will be dispensed for a 4 weekly visit, with a 2 day overage. Patients will be administered olaparib capsules orally at a dose of 400 mg twice daily. Eight 50 mg olaparib capsules should be taken at the same time each day approximately 12 hours apart with approximately 240 mL of water.

Other Name: Lynparza

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was conducted in 8 countries 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 Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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).

Reporting Groups

	Description
Overall BRCAm	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.
HRRm^	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^).
Unassigned (not BRCAm, not HRRm^)	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.

Participant Flow: Overall Study

	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
Unspecified	0	2	0
Lost to Follow-up	10	0	1
Death	48	8	1
Eligibility criteria not fulfilled	0	0	1
Patient decision	37	8	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

All patients in the FAS (enrolled and assigned olaparib) were included in the baseline analysis. Where a patient did not meet all the eligibility criteria but was enrolled in error, they were still a part of the FAS.

Reporting Groups

	Description
Overall BRCAm	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.
HRRm^	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^).
Unassigned (not BRCAm, not HRRm^)	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.

Baseline Measures

	Overall BRCAm	HRRm^	Unassigned (not BRCAm, not HRRm^)	Total
Number of Participants [units: Participants]	145	33	3	181
Age Continuous [units: years] Mean ± Standard Deviation	60.1 ± 10.75	62.2 ± 9.74	58.7 ± 9.07	60.5 ± 10.52
Age, Customized [units: Participants]
<35 years	0	0	0	0
≥35 to <50 years	27	3	0	30
≥50 to <65 years	54	13	2	69
≥65 to <80 years	48	15	1	64
≥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: Participants]
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: Participants]
Hispanic or Latino	3	1	0	4
Not Hispanic or Latino	142	31	3	176
Unknown or Not Reported	0	1	0	1

Outcome Measures

1. Primary Outcome Measure: Progression-Free Survival (PFS) [ Time Frame: 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). ]

Measure Type	Primary
Measure Name	Progression-Free Survival (PFS)
Measure Description	To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of PFS. The PFS was defined as the time from the date of enrolment until date of objective radiological disease progression (assessed by the Investigator via Response Evaluation Criteria in Solid Tumors, version 1.1 [RECIST 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.
Time Frame	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).
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all enrolled patients who were assigned olaparib. The primary endpoint results for PFS assessment included only BRCAm and sBRCAm patients.

Reporting Groups

	Description
Overall BRCAm	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.
sBRCAm	Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had sBRCAm disease (i.e. confirmed somatic mutation).

Measured Values

	Overall BRCAm	sBRCAm
Number of Participants Analyzed [units:participants]	145	55
Progression-Free Survival (PFS) [units: months] Median (95% Confidence Interval)	18.0 (14.3 to 22.1)	16.6 (12.4 to 22.2)

No statistical analysis provided for Progression-Free Survival (PFS)

2. Secondary Outcome Measure: Overall Survival (OS); Assessed at Primary Analysis [ Time Frame: From baseline until death due to any cause. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months). ]

Measure Type	Secondary
Measure Name	Overall Survival (OS); Assessed at Primary Analysis
Measure 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. 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).
Time Frame	From baseline until death due to any cause. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months).
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for OS assessment included only BRCAm and sBRCAm patients.

Reporting Groups

	Description
Overall BRCAm	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 confirmed.
sBRCAm	Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had sBRCAm disease (i.e. confirmed somatic mutation).

Measured Values

	Overall BRCAm	sBRCAm
Number of Participants Analyzed [units:participants]	145	55
Overall Survival (OS); Assessed at Primary Analysis [units: months] Median (95% Confidence Interval)	47.6 (36.1 to NA) ^[1]	NA (33.2 to NA) ^[1]

No statistical analysis provided for Overall Survival (OS); Assessed at Primary Analysis

3. Secondary Outcome Measure: Time to Second Progression (PFS2) or Death; Assessed at Primary Analysis [ Time Frame: 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). ]

Measure Type	Secondary
Measure Name	Time to Second Progression (PFS2) or Death; Assessed at Primary Analysis
Measure 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, 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).
Time Frame	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).
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for PFS2 assessment included only BRCAm and sBRCAm patients.

Reporting Groups

	Description
Overall BRCAm	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 confirmed.
sBRCAm	Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had sBRCAm disease (i.e. confirmed somatic mutation).

Measured Values

	Overall BRCAm	sBRCAm
Number of Participants Analyzed [units:participants]	145	55
Time to Second Progression (PFS2) or Death; Assessed at Primary Analysis [units: months] Median (95% Confidence Interval)	30.9 (24.7 to 40.0)	24.7 (21.8 to 36.1)

No statistical analysis provided for Time to Second Progression (PFS2) or Death; Assessed at Primary Analysis

4. Secondary Outcome Measure: Time to First Subsequent Therapy (Treatment) or Death (TFST); Assessed at Primary Analysis [ Time Frame: 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). ]

Measure Type	Secondary
Measure Name	Time to First Subsequent Therapy (Treatment) or Death (TFST); Assessed at Primary Analysis
Measure 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).
Time Frame	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).
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for TFST assessment included only BRCAm and sBRCAm patients.

Reporting Groups

	Description
Overall BRCAm	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 confirmed.
sBRCAm	Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had sBRCAm disease (i.e. confirmed somatic mutation).

Measured Values

	Overall BRCAm	sBRCAm
Number of Participants Analyzed [units:participants]	145	55
Time to First Subsequent Therapy (Treatment) or Death (TFST); Assessed at Primary Analysis [units: months] Median (95% Confidence Interval)	37.6 (23.5 to 47.6)	31.5 (19.5 to NA) ^[1]

No statistical analysis provided for Time to First Subsequent Therapy (Treatment) or Death (TFST); Assessed at Primary Analysis

5. Secondary Outcome Measure: Time to Second Subsequent Therapy (Treatment) or Death (TSST); Assessed at Primary Analysis [ Time Frame: 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). ]

Measure Type	Secondary
Measure Name	Time to Second Subsequent Therapy (Treatment) or Death (TSST); Assessed at Primary Analysis
Measure 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).
Time Frame	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).
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for TSST assessment included only BRCAm and sBRCAm patients.

Reporting Groups

	Description
Overall BRCAm	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 confirmed.
sBRCAm	Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had sBRCAm disease (i.e. confirmed somatic mutation).

Measured Values

	Overall BRCAm	sBRCAm
Number of Participants Analyzed [units:participants]	145	55
Time to Second Subsequent Therapy (Treatment) or Death (TSST); Assessed at Primary Analysis [units: months] Median (95% Confidence Interval)	47.6 (29.4 to NA) ^[1]	NA (24.7 to NA) ^[1]

No statistical analysis provided for Time to Second Subsequent Therapy (Treatment) or Death (TSST); Assessed at Primary Analysis

6. Secondary Outcome Measure: Time to Discontinuation of Treatment or Death (TDT) [ Time Frame: From enrolment to study treatment discontinuation or death (up to maximum of 6 years). ]

Measure Type	Secondary
Measure Name	Time to Discontinuation of Treatment or Death (TDT)
Measure 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.
Time Frame	From enrolment to study treatment discontinuation or death (up to maximum of 6 years).
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for TDT assessment included only BRCAm and sBRCAm patients.

Reporting Groups

	Description
Overall BRCAm	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 confirmed.
sBRCAm	Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had sBRCAm disease (i.e. confirmed somatic mutation).

Measured Values

	Overall BRCAm	sBRCAm
Number of Participants Analyzed [units:participants]	145	55
Time to Discontinuation of Treatment or Death (TDT) [units: months] Median (95% Confidence Interval)	19.8 (14.3 to 22.9)	19.0 (13.5 to 22.8)

No statistical analysis provided for Time to Discontinuation of Treatment or Death (TDT)

7. Secondary Outcome Measure: Change from Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time [ Time Frame: QoL questionnaires at baseline, Day 29 (Week 4), then every 12 weeks for 24 months or DCO for primary analysis, whichever came first. QoL questionnaires also collected at discontinuation of study treatment visit and 30 days post last dose. ]

Measure Type	Secondary
Measure Name	Change from Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time
Measure Description	To assess the Quality of Life (QoL) of patients with BRCAm and sBRCAm ovarian cancer by evaluation of 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.
Time Frame	QoL questionnaires at baseline, Day 29 (Week 4), then every 12 weeks for 24 months or DCO for primary analysis, whichever came first. QoL questionnaires also collected at discontinuation of study treatment visit and 30 days post last dose.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Overall BRCAm	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 confirmed.
sBRCAm	Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had sBRCAm disease (i.e. confirmed somatic mutation).

Measured Values

	Overall BRCAm	sBRCAm
Number of Participants Analyzed [units:participants]	131	50
Change from Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time [units: scores on a scale] Mean (Standard Deviation)
Week 4	-2.2 (9.82)	-1.9 (9.59)
Week 16	-1.3 (10.04)	-0.3 (10.85)
Week 28	1.2 (9.44)	3.2 (10.25)
Week 40	1.6 (10.72)	4.1 (10.48)
Week 52	3.2 (9.03)	4.9 (7.84)
Week 64	1.8 (9.88)	0.8 (9.72)
Week 76	1.4 (9.27)	0.3 (9.83)
Week 88	2.0 (9.97)	1.5 (10.86)
Week 100	-0.2 (9.41)	-3.5 (7.54)
Discontinuation of olaparib visit	-4.7 (13.00)	-7.4 (15.53)
30 days post discontinuation	-8.0 (13.45)	-4.3 (13.36)

No statistical analysis provided for Change from Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time

8. Secondary Outcome Measure: Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time [ Time Frame: QoL questionnaires at baseline, Day 29 (Week 4), then every 12 weeks for 24 months or DCO for primary analysis, whichever came first. QoL questionnaires also collected at discontinuation of study treatment visit and 30 days post last dose. ]

Measure Type	Secondary
Measure Name	Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time
Measure 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.
Time Frame	QoL questionnaires at baseline, Day 29 (Week 4), then every 12 weeks for 24 months or DCO for primary analysis, whichever came first. QoL questionnaires also collected at discontinuation of study treatment visit and 30 days post last dose.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Overall BRCAm	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 confirmed.
sBRCAm	Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had sBRCAm disease (i.e. confirmed somatic mutation).

Measured Values

	Overall BRCAm	sBRCAm
Number of Participants Analyzed [units:participants]	136	53
Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time [units: scores on a scale] Mean (Standard Deviation)
Week 4	-2.9 (8.21)	-2.9 (7.58)
Week 16	-2.5 (7.54)	-2.7 (9.26)
Week 28	-1.2 (7.95)	-0.6 (7.25)
Week 40	-0.3 (7.91)	0.9 (7.02)
Week 52	0.6 (7.43)	1.3 (7.25)
Week 64	0.8 (7.26)	0.5 (8.47)
Week 76	-0.3 (8.57)	-1.1 (8.74)
Week 88	0.3 (8.45)	-0.9 (5.81)
Week 100	-0.4 (8.59)	-1.3 (8.75)
Discontinuation of olaparib visit	-2.3 (9.01)	-2.7 (9.32)
30 days post discontinuation	-5.2 (11.16)	-3.8 (9.65)

No statistical analysis provided for Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time

9. Secondary Outcome Measure: Change from Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time [ Time Frame: FLIE questionnaires at baseline, weekly until Day 29 (Week 4), then every 12 weeks for 24 months or DCO for primary analysis, whichever came first. FLIE questionnaires also collected at discontinuation of study treatment visit and 30 days post last dose. ]

Measure Type	Secondary
Measure Name	Change from Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time
Measure 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.
Time Frame	FLIE questionnaires at baseline, weekly until Day 29 (Week 4), then every 12 weeks for 24 months or DCO for primary analysis, whichever came first. FLIE questionnaires also collected at discontinuation of study treatment visit and 30 days post last dose.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Overall BRCAm	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 confirmed.
sBRCAm	Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had sBRCAm disease (i.e. confirmed somatic mutation).

Measured Values

	Overall BRCAm	sBRCAm
Number of Participants Analyzed [units:participants]	114	46
Change from Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time [units: scores on a scale] Mean (Standard Deviation)
Week 1	-6.1 (18.62)	-1.6 (18.28)
Week 2	-4.5 (18.40)	-2.6 (15.97)
Week 3	-4.1 (14.57)	-3.9 (13.23)
Week 4	-4.8 (18.48)	-5.4 (19.92)
Week 16	-2.3 (11.50)	-6.3 (11.00)
Week 28	-1.6 (13.87)	-3.0 (7.94)
Week 40	-0.1 (14.07)	-3.2 (14.56)
Week 52	0.9 (14.41)	-1.9 (11.64)
Week 64	-0.2 (15.93)	-1.0 (20.77)
Week 76	0.9 (14.14)	0.6 (6.60)
Week 88	2.2 (10.04)	-1.3 (9.29)
Week 100	0.4 (10.37)	0.1 (13.19)
Discontinuation of olaparib visit	-0.7 (20.17)	-8.8 (21.57)
30 days post discontinuation	-5.2 (17.02)	-5.6 (15.69)

No statistical analysis provided for Change from Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time

10. Secondary Outcome Measure: OS; Assessed at Final Analysis [ Time Frame: From baseline until death due to any cause (up to maximum of 6 years). ]

Measure Type	Secondary
Measure Name	OS; Assessed at Final Analysis
Measure 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.
Time Frame	From baseline until death due to any cause (up to maximum of 6 years).
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for OS assessment included only BRCAm and sBRCAm patients.

Reporting Groups

	Description
Overall BRCAm	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 confirmed.
sBRCAm	Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had sBRCAm disease (i.e. confirmed somatic mutation).

Measured Values

	Overall BRCAm	sBRCAm
Number of Participants Analyzed [units:participants]	145	55
OS; Assessed at Final Analysis [units: months] Median (95% Confidence Interval)	46.8 (37.9 to 54.4)	43.2 (31.7 to NA) ^[1]

No statistical analysis provided for OS; Assessed at Final Analysis

11. Secondary Outcome Measure: PFS2 or Death; Assessed at Final Analysis [ Time Frame: 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). ]

Measure Type	Secondary
Measure Name	PFS2 or Death; Assessed at Final Analysis
Measure 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.
Time Frame	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).
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for PFS2 assessment included only BRCAm and sBRCAm patients.

Reporting Groups

	Description
Overall BRCAm	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 confirmed.
sBRCAm	Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had sBRCAm disease (i.e. confirmed somatic mutation).

Measured Values

	Overall BRCAm	sBRCAm
Number of Participants Analyzed [units:participants]	145	55
PFS2 or Death; Assessed at Final Analysis [units: months] Median (95% Confidence Interval)	34.0 (29.3 to 44.2)	29.3 (23.7 to 44.2)

No statistical analysis provided for PFS2 or Death; Assessed at Final Analysis

12. Secondary Outcome Measure: TFST; Assessed at Final Analysis [ Time Frame: From enrolment to first subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation (up to maximum of 6 years). ]

Measure Type	Secondary
Measure Name	TFST; Assessed at Final Analysis
Measure 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.
Time Frame	From enrolment to first subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation (up to maximum of 6 years).
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for TFST assessment included only BRCAm and sBRCAm patients.

Reporting Groups

	Description
Overall BRCAm	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 confirmed.
sBRCAm	Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had sBRCAm disease (i.e. confirmed somatic mutation).

Measured Values

	Overall BRCAm	sBRCAm
Number of Participants Analyzed [units:participants]	145	55
TFST; Assessed at Final Analysis [units: months] Median (95% Confidence Interval)	32.1 (25.8 to 40.0)	31.7 (18.0 to NA) ^[1]

No statistical analysis provided for TFST; Assessed at Final Analysis

13. Secondary Outcome Measure: TSST; Assessed at Final Analysis [ Time Frame: From enrolment to second subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation (up to maximum of 6 years). ]

Measure Type	Secondary
Measure Name	TSST; Assessed at Final Analysis
Measure 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.
Time Frame	From enrolment to second subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation (up to maximum of 6 years).
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for TSST assessment included only BRCAm and sBRCAm patients.

Reporting Groups

	Description
Overall BRCAm	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 confirmed.
sBRCAm	Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had sBRCAm disease (i.e. confirmed somatic mutation).

Measured Values

	Overall BRCAm	sBRCAm
Number of Participants Analyzed [units:participants]	145	55
TSST; Assessed at Final Analysis [units: months] Median (95% Confidence Interval)	38.4 (31.5 to NA) ^[1]	32.1 (25.8 to 44.7)

No statistical analysis provided for TSST; Assessed at Final Analysis

Serious Adverse Events

Time Frame	From first dose of olaparib up to and including 30 days following the date of discontinuation of olaparib. Maximum timeframe of approximately 6 years.
Additional Description	Adverse events are reported for the safety analysis set which included all patients who received at least one dose of olaparib. All- cause mortality was determined for patients in the FAS (enrolled and assigned olaparib).

Reporting Groups

	Description
gBRCAm	Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had gBRCAm disease (i.e. confirmed germline mutation).
sBRCAm	Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had sBRCAm disease (i.e. confirmed somatic mutation).
Overall BRCAm	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.
HRRm	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^).
Unassigned (not BRCAm, not HRRm^)	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, serious adverse events

# participants affected / at risk

27/87 (31.03%)

13/55 (23.64%)

40/143 (27.97%)

7/32 (21.88%)

1/2 (50.00%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

7/87 (8.05%)

5/55 (9.09%)

12/143 (8.39%)

1/32 (3.13%)

0/2 (0.00%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

0/87 (0.00%)

0/55 (0.00%)

0/143 (0.00%)

1/32 (3.13%)

0/2 (0.00%)

# events

Cardiac disorders

Angina unstable¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Cardiac disorders

Atrial fibrillation¹,^†

# participants affected / at risk

0/87 (0.00%)

1/55 (1.82%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Cardiac disorders

Cardiac failure¹,^†

# participants affected / at risk

0/87 (0.00%)

1/55 (1.82%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Cardiac disorders

Myocardial infarction¹,^†

# participants affected / at risk

0/87 (0.00%)

0/55 (0.00%)

0/143 (0.00%)

1/32 (3.13%)

0/2 (0.00%)

# events

Eye disorders

Glaucoma¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Gastrointestinal disorders

Mesenteric vein thrombosis¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

General disorders and administration site conditions

Sudden death¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Infections and infestations

Colonic abscess¹,^†

# participants affected / at risk

0/87 (0.00%)

1/55 (1.82%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

0/87 (0.00%)

1/55 (1.82%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Hepatobiliary disorders

Biliary colic¹,^†

# participants affected / at risk

0/87 (0.00%)

1/55 (1.82%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

3/87 (3.45%)

0/55 (0.00%)

3/143 (2.10%)

1/32 (3.13%)

0/2 (0.00%)

# events

Infections and infestations

Lower respiratory tract infection¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Injury, poisoning and procedural complications

Procedural pain¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Injury, poisoning and procedural complications

Femoral neck fracture¹,^†

# participants affected / at risk

0/87 (0.00%)

1/55 (1.82%)

1/143 (0.70%)

1/32 (3.13%)

0/2 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Acute myeloid leukaemia¹,^†

# participants affected / at risk

2/87 (2.30%)

0/55 (0.00%)

2/143 (1.40%)

0/32 (0.00%)

0/2 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Burkitt's lymphoma¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Papillary thyroid cancer¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Nervous system disorders

Dysarthria¹,^†

# participants affected / at risk

0/87 (0.00%)

1/55 (1.82%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹,^†

# participants affected / at risk

0/87 (0.00%)

0/55 (0.00%)

0/143 (0.00%)

1/32 (3.13%)

0/2 (0.00%)

# events

Nervous system disorders

Transient ischaemic attack¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Vascular disorders

Deep vein thrombosis¹,^†

# participants affected / at risk

0/87 (0.00%)

1/55 (1.82%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Ear and labyrinth disorders

Vertigo¹,^†

# participants affected / at risk

0/87 (0.00%)

0/55 (0.00%)

0/143 (0.00%)

1/32 (3.13%)

0/2 (0.00%)

# events

Gastrointestinal disorders

Abdominal hernia¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Gastrointestinal disorders

Small intestinal obstruction¹,^†

# participants affected / at risk

0/87 (0.00%)

1/55 (1.82%)

1/143 (0.70%)

0/32 (0.00%)

1/2 (50.00%)

# events

Gastrointestinal disorders

Subileus¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

0/87 (0.00%)

1/55 (1.82%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Immune system disorders

Contrast media allergy¹,^†

# participants affected / at risk

0/87 (0.00%)

1/55 (1.82%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Immune system disorders

Drug hypersensitivity¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Infections and infestations

Gastroenteritis viral¹,^†

# participants affected / at risk

0/87 (0.00%)

0/55 (0.00%)

0/143 (0.00%)

1/32 (3.13%)

0/2 (0.00%)

# events

Infections and infestations

Sepsis¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Investigations

Platelet count decreased¹,^†

# participants affected / at risk

0/87 (0.00%)

1/55 (1.82%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to central nervous system¹,^†

# participants affected / at risk

0/87 (0.00%)

1/55 (1.82%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Myelodysplastic syndrome¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Non-hodgkin's lymphoma¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

0/32 (0.00%)

0/2 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹,^†

# participants affected / at risk

3/87 (3.45%)

0/55 (0.00%)

3/143 (2.10%)

1/32 (3.13%)

0/2 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 23.0

Other Adverse Events

Time Frame	From first dose of olaparib up to and including 30 days following the date of discontinuation of olaparib. Maximum timeframe of approximately 6 years.
Additional Description	Adverse events are reported for the safety analysis set which included all patients who received at least one dose of olaparib. All- cause mortality was determined for patients in the FAS (enrolled and assigned olaparib).

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
gBRCAm	Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had gBRCAm disease (i.e. confirmed germline mutation).
sBRCAm	Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had sBRCAm disease (i.e. confirmed somatic mutation).
Overall BRCAm	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.
HRRm	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^).
Unassigned (not BRCAm, not HRRm^)	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.

Other Adverse Events

gBRCAm

sBRCAm

Overall BRCAm

HRRm

Unassigned (not BRCAm, not HRRm^)

Total, other (not including serious) adverse events

# participants affected / at risk

79/87 (90.80%)

51/55 (92.73%)

131/143 (91.61%)

29/32 (90.63%)

1/2 (50.00%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

38/87 (43.68%)

19/55 (34.55%)

57/143 (39.86%)

11/32 (34.38%)

1/2 (50.00%)

# events

Blood and lymphatic system disorders

Leukopenia¹,^†

# participants affected / at risk

6/87 (6.90%)

2/55 (3.64%)

8/143 (5.59%)

0/32 (0.00%)

0/2 (0.00%)

# events

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

12/87 (13.79%)

4/55 (7.27%)

16/143 (11.19%)

1/32 (3.13%)

0/2 (0.00%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

5/87 (5.75%)

6/55 (10.91%)

11/143 (7.69%)

1/32 (3.13%)

0/2 (0.00%)

# events

Gastrointestinal disorders

Abdominal distension¹,^†

# participants affected / at risk

6/87 (6.90%)

2/55 (3.64%)

8/143 (5.59%)

3/32 (9.38%)

0/2 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

11/87 (12.64%)

12/55 (21.82%)

23/143 (16.08%)

8/32 (25.00%)

0/2 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain lower¹,^†

# participants affected / at risk

3/87 (3.45%)

0/55 (0.00%)

3/143 (2.10%)

3/32 (9.38%)

0/2 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain upper¹,^†

# participants affected / at risk

9/87 (10.34%)

4/55 (7.27%)

13/143 (9.09%)

0/32 (0.00%)

0/2 (0.00%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

5/87 (5.75%)

8/55 (14.55%)

13/143 (9.09%)

5/32 (15.63%)

0/2 (0.00%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

15/87 (17.24%)

9/55 (16.36%)

24/143 (16.78%)

8/32 (25.00%)

0/2 (0.00%)

# events

Gastrointestinal disorders

Gastrooesophageal reflux disease¹,^†

# participants affected / at risk

3/87 (3.45%)

0/55 (0.00%)

3/143 (2.10%)

2/32 (6.25%)

1/2 (50.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

49/87 (56.32%)

28/55 (50.91%)

78/143 (54.55%)

19/32 (59.38%)

0/2 (0.00%)

# events

123

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

24/87 (27.59%)

14/55 (25.45%)

38/143 (26.57%)

10/32 (31.25%)

1/2 (50.00%)

# events

General disorders and administration site conditions

Asthenia¹,^†

# participants affected / at risk

13/87 (14.94%)

11/55 (20.00%)

24/143 (16.78%)

2/32 (6.25%)

0/2 (0.00%)

# events

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

38/87 (43.68%)

22/55 (40.00%)

60/143 (41.96%)

15/32 (46.88%)

1/2 (50.00%)

# events

General disorders and administration site conditions

Influenza like illness¹,^†

# participants affected / at risk

7/87 (8.05%)

2/55 (3.64%)

9/143 (6.29%)

0/32 (0.00%)

0/2 (0.00%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

5/87 (5.75%)

1/55 (1.82%)

6/143 (4.20%)

0/32 (0.00%)

0/2 (0.00%)

# events

Infections and infestations

Influenza¹,^†

# participants affected / at risk

7/87 (8.05%)

0/55 (0.00%)

7/143 (4.90%)

0/32 (0.00%)

0/2 (0.00%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

9/87 (10.34%)

3/55 (5.45%)

12/143 (8.39%)

2/32 (6.25%)

0/2 (0.00%)

# events

Infections and infestations

Respiratory tract infection¹,^†

# participants affected / at risk

0/87 (0.00%)

3/55 (5.45%)

3/143 (2.10%)

2/32 (6.25%)

0/2 (0.00%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

2/87 (2.30%)

6/55 (10.91%)

8/143 (5.59%)

1/32 (3.13%)

0/2 (0.00%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

5/87 (5.75%)

6/55 (10.91%)

11/143 (7.69%)

4/32 (12.50%)

0/2 (0.00%)

# events

Injury, poisoning and procedural complications

Foot fracture¹,^†

# participants affected / at risk

0/87 (0.00%)

0/55 (0.00%)

0/143 (0.00%)

0/32 (0.00%)

1/2 (50.00%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

7/87 (8.05%)

1/55 (1.82%)

8/143 (5.59%)

1/32 (3.13%)

0/2 (0.00%)

# events

Investigations

Blood creatinine increased¹,^†

# participants affected / at risk

8/87 (9.20%)

3/55 (5.45%)

11/143 (7.69%)

4/32 (12.50%)

0/2 (0.00%)

# events

Investigations

Glomerular filtration rate decreased¹,^†

# participants affected / at risk

2/87 (2.30%)

3/55 (5.45%)

5/143 (3.50%)

0/32 (0.00%)

0/2 (0.00%)

# events

Investigations

Neutrophil count decreased¹,^†

# participants affected / at risk

5/87 (5.75%)

2/55 (3.64%)

7/143 (4.90%)

1/32 (3.13%)

1/2 (50.00%)

# events

Investigations

Platelet count decreased¹,^†

# participants affected / at risk

5/87 (5.75%)

1/55 (1.82%)

6/143 (4.20%)

1/32 (3.13%)

0/2 (0.00%)

# events

Investigations

White blood cell count decreased¹,^†

# participants affected / at risk

5/87 (5.75%)

2/55 (3.64%)

7/143 (4.90%)

1/32 (3.13%)

0/2 (0.00%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

10/87 (11.49%)

7/55 (12.73%)

17/143 (11.89%)

5/32 (15.63%)

0/2 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

7/87 (8.05%)

4/55 (7.27%)

11/143 (7.69%)

3/32 (9.38%)

0/2 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹,^†

# participants affected / at risk

4/87 (4.60%)

5/55 (9.09%)

9/143 (6.29%)

0/32 (0.00%)

0/2 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

4/87 (4.60%)

1/55 (1.82%)

5/143 (3.50%)

2/32 (6.25%)

0/2 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹,^†

# participants affected / at risk

4/87 (4.60%)

2/55 (3.64%)

6/143 (4.20%)

3/32 (9.38%)

0/2 (0.00%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

13/87 (14.94%)

2/55 (3.64%)

15/143 (10.49%)

5/32 (15.63%)

0/2 (0.00%)

# events

Nervous system disorders

Dysgeusia¹,^†

# participants affected / at risk

8/87 (9.20%)

3/55 (5.45%)

11/143 (7.69%)

4/32 (12.50%)

0/2 (0.00%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

11/87 (12.64%)

3/55 (5.45%)

14/143 (9.79%)

6/32 (18.75%)

0/2 (0.00%)

# events

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

4/87 (4.60%)

3/55 (5.45%)

7/143 (4.90%)

0/32 (0.00%)

0/2 (0.00%)

# events

Psychiatric disorders

Depression¹,^†

# participants affected / at risk

4/87 (4.60%)

3/55 (5.45%)

7/143 (4.90%)

1/32 (3.13%)

0/2 (0.00%)

# events

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

7/87 (8.05%)

4/55 (7.27%)

11/143 (7.69%)

1/32 (3.13%)

0/2 (0.00%)

# events

Psychiatric disorders

Irritability¹,^†

# participants affected / at risk

0/87 (0.00%)

0/55 (0.00%)

0/143 (0.00%)

0/32 (0.00%)

1/2 (50.00%)

# events

Gastrointestinal disorders

Dyspepsia¹,^†

# participants affected / at risk

14/87 (16.09%)

8/55 (14.55%)

23/143 (16.08%)

5/32 (15.63%)

0/2 (0.00%)

# events

Gastrointestinal disorders

Haemorrhoids¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

2/32 (6.25%)

0/2 (0.00%)

# events

General disorders and administration site conditions

Mucosal inflammation¹,^†

# participants affected / at risk

1/87 (1.15%)

3/55 (5.45%)

4/143 (2.80%)

1/32 (3.13%)

0/2 (0.00%)

# events

General disorders and administration site conditions

Oedema peripheral¹,^†

# participants affected / at risk

0/87 (0.00%)

6/55 (10.91%)

6/143 (4.20%)

1/32 (3.13%)

0/2 (0.00%)

# events

General disorders and administration site conditions

Peripheral swelling¹,^†

# participants affected / at risk

5/87 (5.75%)

2/55 (3.64%)

7/143 (4.90%)

0/32 (0.00%)

0/2 (0.00%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

6/87 (6.90%)

2/55 (3.64%)

8/143 (5.59%)

2/32 (6.25%)

0/2 (0.00%)

# events

Infections and infestations

Oral candidiasis¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

2/32 (6.25%)

0/2 (0.00%)

# events

Metabolism and nutrition disorders

Hypomagnesaemia¹,^†

# participants affected / at risk

6/87 (6.90%)

2/55 (3.64%)

8/143 (5.59%)

2/32 (6.25%)

0/2 (0.00%)

# events

Metabolism and nutrition disorders

Vitamin d deficiency¹,^†

# participants affected / at risk

2/87 (2.30%)

3/55 (5.45%)

5/143 (3.50%)

0/32 (0.00%)

0/2 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

11/87 (12.64%)

6/55 (10.91%)

17/143 (11.89%)

0/32 (0.00%)

0/2 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Muscle spasms¹,^†

# participants affected / at risk

0/87 (0.00%)

1/55 (1.82%)

1/143 (0.70%)

2/32 (6.25%)

0/2 (0.00%)

# events

Nervous system disorders

Taste disorder¹,^†

# participants affected / at risk

0/87 (0.00%)

0/55 (0.00%)

0/143 (0.00%)

0/32 (0.00%)

1/2 (50.00%)

# events

Psychiatric disorders

Personality change¹,^†

# participants affected / at risk

0/87 (0.00%)

0/55 (0.00%)

0/143 (0.00%)

0/32 (0.00%)

1/2 (50.00%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

9/87 (10.34%)

5/55 (9.09%)

14/143 (9.79%)

6/32 (18.75%)

0/2 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

9/87 (10.34%)

4/55 (7.27%)

13/143 (9.09%)

6/32 (18.75%)

0/2 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain¹,^†

# participants affected / at risk

3/87 (3.45%)

1/55 (1.82%)

4/143 (2.80%)

2/32 (6.25%)

0/2 (0.00%)

# events

Skin and subcutaneous tissue disorders

Alopecia¹,^†

# participants affected / at risk

7/87 (8.05%)

4/55 (7.27%)

11/143 (7.69%)

2/32 (6.25%)

0/2 (0.00%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

4/87 (4.60%)

3/55 (5.45%)

7/143 (4.90%)

1/32 (3.13%)

0/2 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

3/87 (3.45%)

3/55 (5.45%)

6/143 (4.20%)

3/32 (9.38%)

0/2 (0.00%)

# events

Vascular disorders

Deep vein thrombosis¹,^†

# participants affected / at risk

1/87 (1.15%)

0/55 (0.00%)

1/143 (0.70%)

2/32 (6.25%)

0/2 (0.00%)

# events

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

3/87 (3.45%)

3/55 (5.45%)

6/143 (4.20%)

1/32 (3.13%)

0/2 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 23.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

Redacted SAP
Download
Redacted CSP
Download
Synopsis_Primary
Download
Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Sandro Pignata

Istituto Nazionale Tumori Fondazione G. Pascale, 80131, Napoli, Italy

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Redacted SAP

Redacted CSP

Synopsis_Primary

Synopsis

Trial Results Summaries