Trial Outcomes & Findings for To Study Clinical Effectiveness and Safety of Olaparib Monotherapy in Metastatic Breast Cancer Patients. (NCT NCT03286842)

Last Updated: 2023-01-17

Results Overview

The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting through assessment of PFS in germline BRCA mutated patients was evaluated. PFS is defined as the time from first dose of olaparib to the date of progression or death from any cause. In this study, disease progression in gBRCAm patients will be based on Investigator assessment, i.e. radiological ( e.g. RECIST) progression, symptomatic progression, or clear progression of non-measurable disease, as long as progression can be documented.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

256 participants

Primary outcome timeframe

At every visit until the earliest of disease progression, death or end of study (up to 3 years)

Results posted on

2023-01-17

Participant Flow

Participants were enrolled in this study from 17-January-2018 to 21-March-2019 in 125 sites in 15 countries.

Participants who met the inclusion and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment. A total of 256 participants were enrolled in this study but, only 255 started treatment.

Participant milestones

Participant milestones
Measure	Olaparib Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.
Overall Study STARTED	255
Overall Study COMPLETED	175
Overall Study NOT COMPLETED	80

Reasons for withdrawal

Reasons for withdrawal
Measure	Olaparib Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.
Overall Study Patients rolled over to another study	80

Baseline Characteristics

The number analyzed in both the rows sums up to the overall number.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Olaparib n=255 Participants Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.
Race (NIH/OMB) gBRCAm cohort · Unknown or Not Reported	50 Participants n=252 Participants • The number analyzed in both the rows sums up to the overall number.
Race (NIH/OMB) sBRCAm cohort · American Indian or Alaska Native	0 Participants n=3 Participants • The number analyzed in both the rows sums up to the overall number.
Race (NIH/OMB) sBRCAm cohort · Asian	1 Participants n=3 Participants • The number analyzed in both the rows sums up to the overall number.
Race (NIH/OMB) sBRCAm cohort · Native Hawaiian or Other Pacific Islander	0 Participants n=3 Participants • The number analyzed in both the rows sums up to the overall number.
Race (NIH/OMB) sBRCAm cohort · Black or African American	0 Participants n=3 Participants • The number analyzed in both the rows sums up to the overall number.
Race (NIH/OMB) sBRCAm cohort · White	0 Participants n=3 Participants • The number analyzed in both the rows sums up to the overall number.
Race (NIH/OMB) sBRCAm cohort · More than one race	0 Participants n=3 Participants • The number analyzed in both the rows sums up to the overall number.
Race (NIH/OMB) sBRCAm cohort · Unknown or Not Reported	2 Participants n=3 Participants • The number analyzed in both the rows sums up to the overall number.
Age, Continuous Germline BRCA1/2 mutation (gBRCAm) cohort	46.2 years STANDARD_DEVIATION 11.30 • n=252 Participants • The number analyzed in both the rows sums up to the overall number.
Age, Continuous Somatic BRCA1/2 mutation (sBRCAm) cohort	55.3 years STANDARD_DEVIATION 13.01 • n=3 Participants • The number analyzed in both the rows sums up to the overall number.
Sex: Female, Male gBRCAm cohort · Female	248 Participants n=252 Participants • The number analyzed in both the rows sums up to the overall number.
Sex: Female, Male gBRCAm cohort · Male	4 Participants n=252 Participants • The number analyzed in both the rows sums up to the overall number.
Sex: Female, Male sBRCAm cohort · Female	3 Participants n=3 Participants • The number analyzed in both the rows sums up to the overall number.
Sex: Female, Male sBRCAm cohort · Male	0 Participants n=3 Participants • The number analyzed in both the rows sums up to the overall number.
Ethnicity (NIH/OMB) gBRCAm cohort · Hispanic or Latino	13 Participants n=252 Participants • The number analyzed in both the rows sums up to the overall number.
Ethnicity (NIH/OMB) gBRCAm cohort · Not Hispanic or Latino	189 Participants n=252 Participants • The number analyzed in both the rows sums up to the overall number.
Ethnicity (NIH/OMB) gBRCAm cohort · Unknown or Not Reported	50 Participants n=252 Participants • The number analyzed in both the rows sums up to the overall number.
Ethnicity (NIH/OMB) sBRCAm cohort · Hispanic or Latino	0 Participants n=3 Participants • The number analyzed in both the rows sums up to the overall number.
Ethnicity (NIH/OMB) sBRCAm cohort · Not Hispanic or Latino	1 Participants n=3 Participants • The number analyzed in both the rows sums up to the overall number.
Ethnicity (NIH/OMB) sBRCAm cohort · Unknown or Not Reported	2 Participants n=3 Participants • The number analyzed in both the rows sums up to the overall number.
Race (NIH/OMB) gBRCAm cohort · American Indian or Alaska Native	1 Participants n=252 Participants • The number analyzed in both the rows sums up to the overall number.
Race (NIH/OMB) gBRCAm cohort · Asian	22 Participants n=252 Participants • The number analyzed in both the rows sums up to the overall number.
Race (NIH/OMB) gBRCAm cohort · Native Hawaiian or Other Pacific Islander	0 Participants n=252 Participants • The number analyzed in both the rows sums up to the overall number.
Race (NIH/OMB) gBRCAm cohort · Black or African American	2 Participants n=252 Participants • The number analyzed in both the rows sums up to the overall number.
Race (NIH/OMB) gBRCAm cohort · White	177 Participants n=252 Participants • The number analyzed in both the rows sums up to the overall number.
Race (NIH/OMB) gBRCAm cohort · More than one race	0 Participants n=252 Participants • The number analyzed in both the rows sums up to the overall number.

PRIMARY outcome

Timeframe: At every visit until the earliest of disease progression, death or end of study (up to 3 years)

Population: The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.

Outcome measures

Outcome measures
Measure	Olaparib gBRCAm Cohort n=252 Participants Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.	Olaparib sBRCAm Cohort Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.
Progression-free Survival (PFS) in Real-world Setting in Germline BRCA Mutated Participants	8.18 months Interval 6.97 to 9.17	—

SECONDARY outcome

Timeframe: At every visit and until death or end of study (up to 3 years)

Population: The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.

The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of overall survival in germline BRCA mutated participants was determined. OS is defined as the time from first dose of olaparib to the date of death from any cause.

Outcome measures

Outcome measures
Measure	Olaparib gBRCAm Cohort n=252 Participants Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.	Olaparib sBRCAm Cohort Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.
Overall Survival (OS) in Germline BRCA Mutated Participants	24.94 months Interval 21.06 to 28.91	—

SECONDARY outcome

Timeframe: At every visit until start of first subsequent anticancer treatment or death or end of study (up to 3 years)

Population: The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.

Outcome measures

Outcome measures
Measure	Olaparib gBRCAm Cohort n=252 Participants Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.	Olaparib sBRCAm Cohort Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.
Time to First Subsequent Treatment or Death (TFST) in Germline BRCA Mutated Participants	9.40 months Interval 8.61 to 10.64	—

SECONDARY outcome

Timeframe: At every visit until start of second subsequent anticancer treatment or death or end of study (up to 3 years)

Population: The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.

Outcome measures

Outcome measures
Measure	Olaparib gBRCAm Cohort n=252 Participants Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.	Olaparib sBRCAm Cohort Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.
Time to Second Subsequent Treatment or Death (TSST) in Germline BRCA Mutated Participants	14.72 months Interval 13.5 to 17.25	—

SECONDARY outcome

Timeframe: At every visit and until discontinuation of study treatment or death or end of study (up to 3 years)

Population: The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.

Outcome measures

Outcome measures
Measure	Olaparib gBRCAm Cohort n=252 Participants Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.	Olaparib sBRCAm Cohort Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.
Time to Study Treatment Discontinuation or Death (TDT) in Germline BRCA Mutated Participants	7.98 months Interval 6.9 to 8.54	—

SECONDARY outcome

Timeframe: At every visit until second progression or death or end of study (up to 3 years)

Population: The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.

The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. PFS2 is defined as the time from first dose of olaparib to the earliest progression event subsequent to that used for the primary variable PFS or death from any cause. Patients alive and for whom a second disease progression has not been observed will be censored at the last time known to be alive and without a second disease progression. In this study, disease progression in gBRCAm patients will be based on Investigator assessment, i.e. radiological ( e.g. RECIST) progression, symptomatic progression, or clear progression of non-measurable disease, as long as progression can be documented

Outcome measures

Outcome measures
Measure	Olaparib gBRCAm Cohort n=252 Participants Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.	Olaparib sBRCAm Cohort Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.
Time to Second Progression or Death (PFS2) in Germline BRCA Mutated Participants	14.49 months Interval 13.17 to 17.05	—

SECONDARY outcome

Timeframe: At every visit until disease progression or death or end of study (up to 3 years)

Population: The Full Analysis Set consisted of all participants who received at least one dose of study treatment.

The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of clinical response rate and duration of clinical response in germline BRCA mutated participants was determined. CRR is defined as the percentage of patients assessed by the Investigator as responding. Response in gBRCAm patients were based on the Investigator's assessment. Data obtained up until progression, or last evaluable assessment in the absence of progression, will be included in the assessment of CRR. However, any responses, which occurred after a further anticancer therapy was received, will not be included in the numerator for the CRR calculation.

Outcome measures

Outcome measures
Measure	Olaparib gBRCAm Cohort n=252 Participants Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.	Olaparib sBRCAm Cohort Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.
Clinical Response Rate (CRR) in Germline BRCA Mutated Participants	49.6 Percentage of participants Interval 43.3 to 55.9	—

SECONDARY outcome

Timeframe: At every visit until disease progression or death or end of study (up to 3 years)

Population: The Full Analysis Set consisted of all participants who received at least one dose of study treatment.

The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of clinical response rate and duration of clinical response in germline BRCA mutated participants was determined. DoCR is defined as the time from the date the Investigator first assessed the patient as responding to the date the Investigator assessed the patient as progressing or the date of death from any cause. The end of response should coincide with the date of progression or death used for the PFS endpoint. The time of the initial response will be defined as the latest of the dates contributing towards the first visit response. If a patient does not progress following a response, they will be censored at the PFS censoring date.

Outcome measures

Outcome measures
Measure	Olaparib gBRCAm Cohort n=252 Participants Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.	Olaparib sBRCAm Cohort Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.
Duration of Clinical Response (DoCR) in Germline BRCA Mutated Participants	8.0 Months Interval 4.2 to 18.6	—

SECONDARY outcome

Timeframe: From Screening (Day -28 to Day -1) until post DCO [up to 3 years]

Population: The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.

The safety and tolerability of olaparib treatment in HER2-ve metastatic breast cancer patients in a real-word setting was evaluated.

Outcome measures

Outcome measures
Measure	Olaparib gBRCAm Cohort n=252 Participants Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.	Olaparib sBRCAm Cohort n=3 Participants Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE	243 Participants	3 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE casually related to study treatment	214 Participants	3 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE of CTCAE grade 3 or higher	69 Participants	2 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE of CTCAE grade 3 or higher, causally related to study treatment	44 Participants	1 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE with outcome = death	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE with outcome = death, causally related to study treatment	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAE (including events with outcome = death)	32 Participants	1 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAE (including events with outcome = death), causally related to study treatment	10 Participants	0 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE leading to discontinuation of study treatment	16 Participants	0 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE leading to discontinuation of study treatment, causally related to study treatment	11 Participants	0 Participants

Adverse Events

Olaparib gBRCAm Cohort

Serious events: 32 serious events

Other events: 243 other events

Deaths: 140 deaths

Olaparib sBRCAm Cohort

Serious events: 1 serious events

Other events: 3 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca Clinical Study Information Center

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee This document contains trade secrets and confidential commercial information, disclosure of which is prohibited without providing advance notice to AstraZeneca and opportunity to object.
Publication restrictions are in place

Restriction type: OTHER

Measure	Olaparib gBRCAm Cohort n=252 participants at risk Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.	Olaparib sBRCAm Cohort n=3 participants at risk Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.
Metabolism and nutrition disorders Hyperglycaemia	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Psychiatric disorders Anxiety	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Psychiatric disorders Psychiatric decompensation	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Nervous system disorders Epilepsy	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Cardiac disorders Pericardial effusion	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Respiratory, thoracic and mediastinal disorders Lung disorder	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Respiratory, thoracic and mediastinal disorders Pleurisy	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Infections and infestations Abscess	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Infections and infestations COVID-19	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Infections and infestations COVID-19 pneumonia	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Infections and infestations Cellulitis	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Infections and infestations Chest wall abscess	0.40% 1/252 • Number of events 4 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Infections and infestations Device related infection	0.40% 1/252 • Number of events 2 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Infections and infestations H1N1 influenza	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Infections and infestations Influenza	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Infections and infestations Skin infection	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Infections and infestations Urinary tract infection	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Infections and infestations Urosepsis	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Infections and infestations Viral infection	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer stage 0, with cancer in situ	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Blood and lymphatic system disorders Anaemia	2.8% 7/252 • Number of events 10 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Blood and lymphatic system disorders Febrile neutropenia	0.79% 2/252 • Number of events 2 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Blood and lymphatic system disorders Pancytopenia	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Gastrointestinal disorders Ileus paralytic	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Gastrointestinal disorders Nausea	0.40% 1/252 • Number of events 2 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Gastrointestinal disorders Pancreatitis acute	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Gastrointestinal disorders Vomiting	0.79% 2/252 • Number of events 3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Musculoskeletal and connective tissue disorders Back pain	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Musculoskeletal and connective tissue disorders Bone pain	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Musculoskeletal and connective tissue disorders Muscle spasms	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
General disorders Asthenia	0.79% 2/252 • Number of events 2 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
General disorders Non-cardiac chest pain	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
General disorders Pyrexia	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Investigations General physical condition abnormal	0.00% 0/252 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	33.3% 1/3 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Injury, poisoning and procedural complications Head injury	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Injury, poisoning and procedural complications Radiation necrosis	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Injury, poisoning and procedural complications Spinal compression fracture	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Injury, poisoning and procedural complications Spinal fracture	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Infections and infestations Pneumonia	0.40% 1/252 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].

Measure	Olaparib gBRCAm Cohort n=252 participants at risk Participants received olaparib 300 mg tablets orally twice daily continuously given as 2 x 150 mg twice daily.	Olaparib sBRCAm Cohort n=3 participants at risk Participants received olaparib 300 mg tablets per dose level orally twice daily continuously given as 2 x 150 mg twice daily.
Infections and infestations Nasopharyngitis	5.6% 14/252 • Number of events 17 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Infections and infestations Upper respiratory tract infection	5.2% 13/252 • Number of events 14 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Infections and infestations Urinary tract infection	6.3% 16/252 • Number of events 22 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Blood and lymphatic system disorders Anaemia	38.9% 98/252 • Number of events 168 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	33.3% 1/3 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Blood and lymphatic system disorders Leukopenia	8.7% 22/252 • Number of events 37 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Blood and lymphatic system disorders Neutropenia	16.3% 41/252 • Number of events 71 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	33.3% 1/3 • Number of events 6 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Metabolism and nutrition disorders Decreased appetite	12.3% 31/252 • Number of events 36 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Psychiatric disorders Insomnia	6.0% 15/252 • Number of events 15 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Nervous system disorders Dizziness	9.1% 23/252 • Number of events 28 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Nervous system disorders Dysgeusia	6.3% 16/252 • Number of events 18 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Nervous system disorders Headache	18.7% 47/252 • Number of events 103 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	66.7% 2/3 • Number of events 2 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Respiratory, thoracic and mediastinal disorders Cough	13.9% 35/252 • Number of events 40 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	33.3% 1/3 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.3% 21/252 • Number of events 24 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Gastrointestinal disorders Abdominal pain	8.3% 21/252 • Number of events 25 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	33.3% 1/3 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Gastrointestinal disorders Abdominal pain upper	7.5% 19/252 • Number of events 31 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Gastrointestinal disorders Constipation	11.9% 30/252 • Number of events 37 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	100.0% 3/3 • Number of events 3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Gastrointestinal disorders Diarrhoea	21.0% 53/252 • Number of events 72 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	66.7% 2/3 • Number of events 4 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Gastrointestinal disorders Dyspepsia	9.9% 25/252 • Number of events 30 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Gastrointestinal disorders Nausea	55.6% 140/252 • Number of events 236 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	66.7% 2/3 • Number of events 2 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Gastrointestinal disorders Vomiting	26.6% 67/252 • Number of events 111 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Musculoskeletal and connective tissue disorders Arthralgia	15.5% 39/252 • Number of events 55 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	33.3% 1/3 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Musculoskeletal and connective tissue disorders Back pain	11.1% 28/252 • Number of events 32 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	33.3% 1/3 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Musculoskeletal and connective tissue disorders Myalgia	6.7% 17/252 • Number of events 17 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	66.7% 2/3 • Number of events 2 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Musculoskeletal and connective tissue disorders Pain in extremity	8.3% 21/252 • Number of events 24 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
General disorders Asthenia	27.8% 70/252 • Number of events 94 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	66.7% 2/3 • Number of events 3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
General disorders Fatigue	23.4% 59/252 • Number of events 84 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
General disorders Pyrexia	12.3% 31/252 • Number of events 43 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	33.3% 1/3 • Number of events 1 • From Screening (Day -28 to -1) until post DCO [up to 3 years].
Investigations Neutrophil count decreased	5.6% 14/252 • Number of events 18 • From Screening (Day -28 to -1) until post DCO [up to 3 years].	0.00% 0/3 • From Screening (Day -28 to -1) until post DCO [up to 3 years].