Epithelial Ovarian Cancer
Conditions
Keywords
polymerisation inhibitor (PARPi), PARPi re-treatment, BRCA1/2 (+ve), BRCA1/2 (-ve), Olaparib, ovarian cancer, progression free survival (PFS)
Brief summary
The OReO study will be a Phase IIIb, randomised, double-blind, placebo-controlled, multicentre study to assess the efficacy and tolerability of Olaparib retreatment, versus matching placebo, in non-mucinous epithelial ovarian cancer (EOC) patients (including patients with primary peritoneal and/or fallopian tube cancer)
Detailed description
The OReO study will investigate the efficacy and safety of Olaparib maintenance re-treatment in patients with relapsed non-mucinous EOC, who have had disease progression following maintenance therapy with a Polyadenosine 5'diphosphoribose \[poly (ADP ribose)\] polymerisation inhibitor (PARPi) and a complete or partial radiological response to subsequent treatment with platinum-based chemotherapy or may have no evidence of disease (if optimal cytoreductive surgery was conducted prior to chemotherapy), and no evidence of a rising CA-125. Patients will be enrolled on the basis of their breast cancer susceptibility gene (BRCA1, BRCA2) status into one of two cohorts (BRCA1/2 \[+ve\] and BRCA1/2 \[-ve\]). The BRCA1/2 (+ve) and BRCA1/2 (-ve) cohorts will be randomised separately. Within each cohort, patients will be randomised by prospective allocation in a 2:1 ratio (Olaparib: matching placebo).
Interventions
DRUGActive Comparator: Olaparib tablets
Olaparib 300mg Olaparib tablets taken orally twice daily (except where this dose and formulation was previously not tolerated) until objective radiological disease progression as per RECIST 1.1 or as long as in the Investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria.
DRUGPlacebo
Placebo 300mg placebo tablets taken orally twice daily (except where this dose and formulation was previously not tolerated) until objective radiological disease progression as per RECIST 1.1 or as long as in the Investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria.
Sponsors
European Network of Gynaecological Oncological Trial Groups (ENGOT)
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Provision of informed consent prior to any study specific procedures * Female patients ≥18 years of age, with histologically diagnosed relapsed non-mucinous epithelial ovarian cancer (EOC) (including primary peritoneal and/or fallopian tube cancer) (Non-mucinous EOC includes patients with serous, endometrioid, and transitional cell tumours, and those with mixed histology where one of these subtypes is predominant (\>50%). Inclusion of other subtypes should first be discussed with the Medical Monitor). * Documented BRCA1/2 status. * Patients must have received one prior PARPi therapy PARPi therapy includes any agent (including Olaparib) used in a maintenance setting For the BRCA1/2 (+ve) cohort, the duration of first PARPi exposure must have been ≥18 months following a first line of chemotherapy or ≥12 months following a second or subsequent line of chemotherapy For the BRCA1/2 (-ve) cohort, the duration of first PARPi exposure must have been ≥12 months following a first line of chemotherapy or ≥6 months following a second or subsequent line of chemotherapy For the last chemotherapy course immediately prior to randomisation on the study Patients must have received a platinum-based chemotherapy regimen (carboplatin, cisplatin or oxaliplatin) and have received at least 4 cycles of treatment Patients must be, in the opinion of the investigator, in response (partial or complete radiological response) or may have no evidence of disease (if optimal cytoreductive surgery was conducted prior to chemotherapy) and no evidence of a rising CA-125, as defined below, following completion of this chemotherapy course Pre-treatment CA-125 measurements must meet criterion specified below * If the first value is within upper limit of normal (ULN) the patient is eligible to be randomised and a second sample is not required * If the first value is greater than ULN a second assessment must be performed at least 7 days after the first. If the second assessment is ≥ 15% more than the first the patient is not eligible. Patients must not have received bevacizumab during this course of treatment. Bevacizumab use as part of an earlier line of chemotherapy is permitted Patients must not have received any investigational agent during this course of treatment Patients must be randomised within 8 weeks of their last dose of chemotherapy (last dose is the day of the last infusion) * Patients must have normal organ and bone marrow function measured within 28 days of randomization. * Eastern Cooperative Oncology Group performance status 0-1 * Patients must have a life expectancy ≥16 weeks. * Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1 * At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline with computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for repeated assessment. or No measurable disease following a complete response to most recent chemotherapy (+/- surgery) * A formalin fixed, paraffin embedded (FFPE) tumour sample from the cancer of sufficient quantity and quality (as specified in the Covance Central Laboratory Services Manual) must be available for future central testing of tumour genetic status. * For inclusion in the optional biomarker research, patients must sign an informed consent for biomarker research.
Exclusion criteria
* Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). * Participation in another clinical study with an investigational product during the chemotherapy course immediately prior to randomisation. * Other malignancy within the last 5 years except the ones detailed in the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Progression-free Survival (PFS) | At randomization visit and at every 12 weeks (+/- 7 days) until objective radiological disease progression as determined by the investigator or other discontinuation criteria are met (assessed upto 3.8 years) | PFS (per RECIST 1.1) was defined as the time from randomisation until the date of Investigator assessed objective radiological disease progression or death (by any cause in the absence of disease progression). Objective progression (per RECIST 1.1) is defined as at least a 20% increase in the sum of the diameters of the target lesions and an absolute increase of \>5 mm, or an overall non-target lesion assessment of progression or a new lesion. Patients who have not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Time to Progression by Gynecologic Cancer Intergroup (GCIG) Criteria | At screening (Visit 1) and at every 12 weeks (±7 days), until objective disease progression, based on progressive serial elevation of serum CA-125 according to the GCIG criteria, or until discontinuation for other reasons (assessed upto 3.8 years) | Time to progression by RECIST or CA-125 or death is defined as the time from randomisation to the earlier date of RECIST progression or CA-125 progression or death by any cause. Patients without a CA-125 progression or a RECIST progression who are still alive at the time of analysis will be censored at the time of their last evaluable RECIST assessment and/or their last available CA-125 measurement, whichever is the earliest at the time of analysis. Patients that do not have any evaluable RECIST assessments or any CA-125 results post-randomisation will be censored at the date of randomisation |
| Efficacy: Time to First Subsequent Treatment Commencement (TFST) | From follow-up i.e. 30 days after last dose of study medication till end of study (assessed every 12 weeks upto 3.8 years) | TFST was assessed as time from randomisation to first subsequent treatment commencement or death if this occurs before commencement of first subsequent treatment. Any patient not known to have had a further subsequent therapy or death was censored at the last known time to have not received subsequent therapy |
| Efficacy: Time to Second Subsequent Treatment Commencement (TSST) | From follow-up i.e. 30 days after last dose of study medication till end of study (assessed every 12 weeks upto 3.8 years) | TSST was assessed as time from randomisation to second subsequent treatment commencement or death if this occurs before commencement of second subsequent treatment. Any patient not known to have had a further second subsequent therapy or death was censored at the last known time to have not received second subsequent therapy |
| Efficacy: Overall Survival (OS) | From randomisation till Long-term follow-up (12-weekly beyond 30 days after last dose of study treatment) assessed upto 3.8 years | OS was defined as the time from the date of randomisation until death due to any cause. 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 |
| Efficacy: Change From Baseline in Health-related Quality of Life (HRQoL) | At Baseline, and from Day 1 until objective disease progression (assessed upto 2 years) | Health related quality of life (HRQoL) of Olaparib maintenance retreatment compared to placebo as measured by the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) was determined. HRQoL was analysed using the FACT-O tool by mixed model for repeated measures (MMRM) analysis of the change from baseline in TOI score. FACT-O TOI is scored from O to 100 with higher scores denoting better quality of life. The higher the score, the better the HRQoL. |
| Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | At Baseline and from Day 1 till follow-up i.e. 30 days after last dose of study medication (assessed upto 3.8 years) | All AEs/serious adverse events (SAEs) reported during the study were recorded. |
| Number of Patients With Adverse Event of Special Interest (AESI). | At Baseline and from Day 1 till long-term follow-up i.e. 12-weekly beyond 30 days after last dose of study treatment (assessed upto 3.8 years) | All AESIs reported during the study were recorded. |
| Efficacy: Time to Study Treatment Discontinuation (TDT) | From follow-up 30 days after last dose of study medication till long-term follow-up i.e. 12-weekly beyond 30 days after last dose of study treatment | TDT was assessed as time from randomisation to study treatment discontinuation or death if this occurs before discontinuation of study treatment. Any patient not known to have died at the time of analysis and not known to have discontinued study treatment was censored based on the last recorded date on which the patient was known to be alive |
Countries
Belgium, Canada, Denmark, France, Germany, Israel, Italy, Norway, Poland, Spain, United Kingdom
Participant flow
Recruitment details
This study was conducted at study centres in 11 countries (France, Italy, Spain, Germany, Poland, Belgium, Denmark, Israel, United Kingdom, Norway, and Canada) between 8-Jun-2017 and 15-Feb-2021.
Pre-assignment details
Patients were randomised into 1 of 2 cohorts depending on their known BRCA1/2 status (BRCA1/2 +ve or BRCA1/2-ve). Within each cohort, patients were randomised in a 2 Olaparib:1 placebo ratio. Randomisation was stratified by prior use of bevacizumab and number of prior regimens of platinum-containing chemotherapy.
Participants by arm
| Arm | Count |
|---|---|
| Olaparib (BRCA1/2 +ve) Patients received olaparib 300mg tablets orally twice daily (bd) continuously | 74 |
| Placebo (BRCA +ve) Patients received placebo 300mg tablets administered orally twice daily (bd) continuously | 38 |
| Olaparib (BRCA1/2 -ve) Patients received olaparib 300mg tablets orally twice daily (bd) continuously | 72 |
| Placebo (BRCA 1/2 -ve) Patients received placebo 300mg tablets administered orally twice daily (bd) continuously | 36 |
| Total | 220 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 37 | 22 | 12 | 8 |
| Overall Study | Lost to Follow-up | 2 | 0 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 1 | 4 | 1 |
Baseline characteristics
| Characteristic | Placebo (BRCA +ve) | Olaparib (BRCA1/2 -ve) | Olaparib (BRCA1/2 +ve) | Placebo (BRCA 1/2 -ve) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 61.5 Years STANDARD_DEVIATION 9.22 | 64.2 Years STANDARD_DEVIATION 9.64 | 59.2 Years STANDARD_DEVIATION 9.31 | 63.3 Years STANDARD_DEVIATION 9.05 | 61.9 Years STANDARD_DEVIATION 9.54 |
| Age, Customized < 50 | 3 Participants | 4 Participants | 11 Participants | 1 Participants | 19 Participants |
| Age, Customized ≥ 50 to < 65 | 20 Participants | 29 Participants | 40 Participants | 19 Participants | 108 Participants |
| Age, Customized ≥ 65 to < 75 | 12 Participants | 30 Participants | 20 Participants | 11 Participants | 73 Participants |
| Age, Customized ≥ 75 | 3 Participants | 9 Participants | 3 Participants | 5 Participants | 20 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Hawaiian Native or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Missing Data | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 5 Participants | 3 Participants | 2 Participants | 13 Participants |
| Race/Ethnicity, Customized White | 35 Participants | 66 Participants | 71 Participants | 33 Participants | 205 Participants |
| Sex: Female, Male Female | 38 Participants | 72 Participants | 74 Participants | 36 Participants | 220 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 39 / 74 | 22 / 38 | 15 / 72 | 8 / 36 |
| other Total, other adverse events | 64 / 74 | 33 / 38 | 65 / 72 | 30 / 36 |
| serious Total, serious adverse events | 5 / 74 | 0 / 38 | 11 / 72 | 2 / 36 |
Outcome results
Primary
Efficacy: Progression-free Survival (PFS)
PFS (per RECIST 1.1) was defined as the time from randomisation until the date of Investigator assessed objective radiological disease progression or death (by any cause in the absence of disease progression). Objective progression (per RECIST 1.1) is defined as at least a 20% increase in the sum of the diameters of the target lesions and an absolute increase of \>5 mm, or an overall non-target lesion assessment of progression or a new lesion. Patients who have not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment.
Time frame: At randomization visit and at every 12 weeks (+/- 7 days) until objective radiological disease progression as determined by the investigator or other discontinuation criteria are met (assessed upto 3.8 years)
Population: Full analysis set (FAS) consisted of all randomised patients analysed on an intent-to-treat (ITT) basis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib (BRCA1/2 +ve) | Efficacy: Progression-free Survival (PFS) | 4.3 Months |
| Placebo (BRCA1/2 +ve) | Efficacy: Progression-free Survival (PFS) | 2.8 Months |
| Olaparib (BRCA1/2 -ve) | Efficacy: Progression-free Survival (PFS) | 5.3 Months |
| Placebo (BRCA1/2 -ve) | Efficacy: Progression-free Survival (PFS) | 2.8 Months |
p-value: 0.02295% CI: [0.372, 0.868]Stratified log-rank
p-value: 0.002395% CI: [0.264, 0.708]Stratified log-rank
Secondary
Efficacy: Change From Baseline in Health-related Quality of Life (HRQoL)
Health related quality of life (HRQoL) of Olaparib maintenance retreatment compared to placebo as measured by the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) was determined. HRQoL was analysed using the FACT-O tool by mixed model for repeated measures (MMRM) analysis of the change from baseline in TOI score. FACT-O TOI is scored from O to 100 with higher scores denoting better quality of life. The higher the score, the better the HRQoL.
Time frame: At Baseline, and from Day 1 until objective disease progression (assessed upto 2 years)
Population: The Patient reported outcome (PRO) analysis set consisted of the FAS patients with a baseline PRO assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Olaparib (BRCA1/2 +ve) | Efficacy: Change From Baseline in Health-related Quality of Life (HRQoL) | -1.27 Change in scores | Standard Error 0.55 |
| Placebo (BRCA1/2 +ve) | Efficacy: Change From Baseline in Health-related Quality of Life (HRQoL) | 1.67 Change in scores | Standard Error 0.89 |
| Olaparib (BRCA1/2 -ve) | Efficacy: Change From Baseline in Health-related Quality of Life (HRQoL) | -2.08 Change in scores | Standard Error 0.6 |
| Placebo (BRCA1/2 -ve) | Efficacy: Change From Baseline in Health-related Quality of Life (HRQoL) | 0.58 Change in scores | Standard Error 0.9 |
Secondary
Efficacy: Overall Survival (OS)
OS was defined as the time from the date of randomisation until death due to any cause. 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 randomisation till Long-term follow-up (12-weekly beyond 30 days after last dose of study treatment) assessed upto 3.8 years
Population: FAS consisted of all randomised patients analysed on an ITT basis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib (BRCA1/2 +ve) | Efficacy: Overall Survival (OS) | 20.1 Months |
| Placebo (BRCA1/2 +ve) | Efficacy: Overall Survival (OS) | 20.9 Months |
| Olaparib (BRCA1/2 -ve) | Efficacy: Overall Survival (OS) | 23.2 Months |
| Placebo (BRCA1/2 -ve) | Efficacy: Overall Survival (OS) | 30.2 Months |
Secondary
Efficacy: Time to First Subsequent Treatment Commencement (TFST)
TFST was assessed as time from randomisation to first subsequent treatment commencement or death if this occurs before commencement of first subsequent treatment. Any patient not known to have had a further subsequent therapy or death was censored at the last known time to have not received subsequent therapy
Time frame: From follow-up i.e. 30 days after last dose of study medication till end of study (assessed every 12 weeks upto 3.8 years)
Population: FAS consisted of all randomised patients analysed on an ITT basis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib (BRCA1/2 +ve) | Efficacy: Time to First Subsequent Treatment Commencement (TFST) | 5.8 Months |
| Placebo (BRCA1/2 +ve) | Efficacy: Time to First Subsequent Treatment Commencement (TFST) | 5.1 Months |
| Olaparib (BRCA1/2 -ve) | Efficacy: Time to First Subsequent Treatment Commencement (TFST) | 7.9 Months |
| Placebo (BRCA1/2 -ve) | Efficacy: Time to First Subsequent Treatment Commencement (TFST) | 4.3 Months |
Secondary
Efficacy: Time to Progression by Gynecologic Cancer Intergroup (GCIG) Criteria
Time to progression by RECIST or CA-125 or death is defined as the time from randomisation to the earlier date of RECIST progression or CA-125 progression or death by any cause. Patients without a CA-125 progression or a RECIST progression who are still alive at the time of analysis will be censored at the time of their last evaluable RECIST assessment and/or their last available CA-125 measurement, whichever is the earliest at the time of analysis. Patients that do not have any evaluable RECIST assessments or any CA-125 results post-randomisation will be censored at the date of randomisation
Time frame: At screening (Visit 1) and at every 12 weeks (±7 days), until objective disease progression, based on progressive serial elevation of serum CA-125 according to the GCIG criteria, or until discontinuation for other reasons (assessed upto 3.8 years)
Population: FAS consisted of all randomised patients analysed on an ITT basis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib (BRCA1/2 +ve) | Efficacy: Time to Progression by Gynecologic Cancer Intergroup (GCIG) Criteria | 2.8 Months |
| Placebo (BRCA1/2 +ve) | Efficacy: Time to Progression by Gynecologic Cancer Intergroup (GCIG) Criteria | 2.8 Months |
| Olaparib (BRCA1/2 -ve) | Efficacy: Time to Progression by Gynecologic Cancer Intergroup (GCIG) Criteria | 2.9 Months |
| Placebo (BRCA1/2 -ve) | Efficacy: Time to Progression by Gynecologic Cancer Intergroup (GCIG) Criteria | 2.79 Months |
Secondary
Efficacy: Time to Second Subsequent Treatment Commencement (TSST)
TSST was assessed as time from randomisation to second subsequent treatment commencement or death if this occurs before commencement of second subsequent treatment. Any patient not known to have had a further second subsequent therapy or death was censored at the last known time to have not received second subsequent therapy
Time frame: From follow-up i.e. 30 days after last dose of study medication till end of study (assessed every 12 weeks upto 3.8 years)
Population: FAS consisted of all randomised patients analysed on an ITT basis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib (BRCA1/2 +ve) | Efficacy: Time to Second Subsequent Treatment Commencement (TSST) | 13.1 Months |
| Placebo (BRCA1/2 +ve) | Efficacy: Time to Second Subsequent Treatment Commencement (TSST) | 11.7 Months |
| Olaparib (BRCA1/2 -ve) | Efficacy: Time to Second Subsequent Treatment Commencement (TSST) | 15.4 Months |
| Placebo (BRCA1/2 -ve) | Efficacy: Time to Second Subsequent Treatment Commencement (TSST) | 12.7 Months |
Secondary
Efficacy: Time to Study Treatment Discontinuation (TDT)
TDT was assessed as time from randomisation to study treatment discontinuation or death if this occurs before discontinuation of study treatment. Any patient not known to have died at the time of analysis and not known to have discontinued study treatment was censored based on the last recorded date on which the patient was known to be alive
Time frame: From follow-up 30 days after last dose of study medication till long-term follow-up i.e. 12-weekly beyond 30 days after last dose of study treatment
Population: FAS consisted of all randomised patients analysed on an ITT basis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib (BRCA1/2 +ve) | Efficacy: Time to Study Treatment Discontinuation (TDT) | 4.5 Months |
| Placebo (BRCA1/2 +ve) | Efficacy: Time to Study Treatment Discontinuation (TDT) | 3.4 Months |
| Olaparib (BRCA1/2 -ve) | Efficacy: Time to Study Treatment Discontinuation (TDT) | 5.6 Months |
| Placebo (BRCA1/2 -ve) | Efficacy: Time to Study Treatment Discontinuation (TDT) | 3.1 Months |
Secondary
Number of Patients With Adverse Event of Special Interest (AESI).
All AESIs reported during the study were recorded.
Time frame: At Baseline and from Day 1 till long-term follow-up i.e. 12-weekly beyond 30 days after last dose of study treatment (assessed upto 3.8 years)
Population: The safety analysis set included all patients who received at least 1 dose of randomised study treatment, Olaparib or placebo
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olaparib (BRCA1/2 +ve) | Number of Patients With Adverse Event of Special Interest (AESI). | 1 Participants |
| Placebo (BRCA1/2 +ve) | Number of Patients With Adverse Event of Special Interest (AESI). | 1 Participants |
| Olaparib (BRCA1/2 -ve) | Number of Patients With Adverse Event of Special Interest (AESI). | 1 Participants |
| Placebo (BRCA1/2 -ve) | Number of Patients With Adverse Event of Special Interest (AESI). | 0 Participants |
Secondary
Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs)
All AEs/serious adverse events (SAEs) reported during the study were recorded.
Time frame: At Baseline and from Day 1 till follow-up i.e. 30 days after last dose of study medication (assessed upto 3.8 years)
Population: The safety analysis set included all patients who received at least 1 dose of randomised study treatment, Olaparib or placebo
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Olaparib (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE leading to discontinuation of study medication, causally related to treatment | 1 Participants |
| Olaparib (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE leading to dose modification, causally related to treatment | 14 Participants |
| Olaparib (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any treatment-emergent SAE (including events with outcome = death), causally related to treatment | 1 Participants |
| Olaparib (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any Treatment emergent adverse event (TEAE) | 64 Participants |
| Olaparib (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE leading to discontinuation of study medication | 2 Participants |
| Olaparib (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher | 11 Participants |
| Olaparib (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE of CTCAE grade 3 or higher, causally related to treatment | 5 Participants |
| Olaparib (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE causally related to treatment | 50 Participants |
| Olaparib (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE leading to dose modification | 18 Participants |
| Olaparib (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE with outcome = death | 0 Participants |
| Olaparib (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE with outcome = death, causally related to treatment | 0 Participants |
| Olaparib (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any treatment-emergent SAE (including events with outcome = death) | 5 Participants |
| Placebo (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE causally related to treatment | 23 Participants |
| Placebo (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any treatment-emergent SAE (including events with outcome = death) | 0 Participants |
| Placebo (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE of CTCAE grade 3 or higher, causally related to treatment | 1 Participants |
| Placebo (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE leading to discontinuation of study medication | 0 Participants |
| Placebo (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE leading to discontinuation of study medication, causally related to treatment | 0 Participants |
| Placebo (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any treatment-emergent SAE (including events with outcome = death), causally related to treatment | 0 Participants |
| Placebo (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any Treatment emergent adverse event (TEAE) | 33 Participants |
| Placebo (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE with outcome = death, causally related to treatment | 0 Participants |
| Placebo (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE with outcome = death | 0 Participants |
| Placebo (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher | 2 Participants |
| Placebo (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE leading to dose modification, causally related to treatment | 5 Participants |
| Placebo (BRCA1/2 +ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE leading to dose modification | 6 Participants |
| Olaparib (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any treatment-emergent SAE (including events with outcome = death), causally related to treatment | 3 Participants |
| Olaparib (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any Treatment emergent adverse event (TEAE) | 66 Participants |
| Olaparib (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE causally related to treatment | 53 Participants |
| Olaparib (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher | 15 Participants |
| Olaparib (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE of CTCAE grade 3 or higher, causally related to treatment | 5 Participants |
| Olaparib (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE with outcome = death | 0 Participants |
| Olaparib (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE with outcome = death, causally related to treatment | 0 Participants |
| Olaparib (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any treatment-emergent SAE (including events with outcome = death) | 11 Participants |
| Olaparib (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE leading to discontinuation of study medication | 1 Participants |
| Olaparib (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE leading to discontinuation of study medication, causally related to treatment | 0 Participants |
| Olaparib (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE leading to dose modification | 28 Participants |
| Olaparib (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE leading to dose modification, causally related to treatment | 21 Participants |
| Placebo (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE with outcome = death, causally related to treatment | 0 Participants |
| Placebo (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE with outcome = death | 0 Participants |
| Placebo (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any Treatment emergent adverse event (TEAE) | 31 Participants |
| Placebo (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE leading to discontinuation of study medication, causally related to treatment | 0 Participants |
| Placebo (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE of CTCAE grade 3 or higher, causally related to treatment | 1 Participants |
| Placebo (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher | 3 Participants |
| Placebo (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE leading to dose modification, causally related to treatment | 1 Participants |
| Placebo (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE leading to dose modification | 2 Participants |
| Placebo (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any treatment-emergent SAE (including events with outcome = death), causally related to treatment | 0 Participants |
| Placebo (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any treatment-emergent SAE (including events with outcome = death) | 2 Participants |
| Placebo (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE causally related to treatment | 14 Participants |
| Placebo (BRCA1/2 -ve) | Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs) | Any TEAE leading to discontinuation of study medication | 0 Participants |