Neoplasms, Breast, Carcinoma of Breast, Human Epidermal Growth Factor 2 Negative Carcinoma of Breast, BRCA1 Gene Mutation, BRCA2 Gene Mutation, Ovarian Neoplasms
Conditions
Keywords
Human Epidermal Growth Factor 2 Negative Carcinoma of Breast, BRCA1 Gene Mutation, BRCA2 Gene Mutation, PARP Inhibitor, BRCA
Brief summary
The purpose of this study is to compare progression-free survival (PFS) in patients with advanced/metastatic breast cancer who have a BRCA mutation when treated with niraparib as compared to those treated with physician's choice
Detailed description
This is a phase III, randomized, open label, multicenter, controlled trial of niraparib versus physician's choice in previously-treated, HER2 negative, germline BRCA mutation-positive breast cancer patients. Niraparib is an orally active PARP inhibitor. Niraparib (in a 2:1 ratio) will be administered once daily continuously during a 21-day cycle. Physician's choice will be administered on a 21-day cycle. Health-related quality of life will be measured. The safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examinations, electrocardiograms (ECGs), and safety laboratory values.
Interventions
DRUGniraparib
300 mg (3x100 mg capsules) once daily until progression or unacceptable toxicity develops
Choice of 4 standard of care metastatic breast cancer chemotherapies, until progression or unacceptable toxicity develops
Sponsors
European Organisation for Research and Treatment of Cancer - EORTC
Breast International Group
Myriad Genetic Laboratories, Inc.
US Oncology Research
Sarah Cannon
Facing Our Risk of Cancer Empowered
Tesaro, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomization will be 2:1 (treatment:control) in at least 215 patients with germline BRCA mutations.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Germline BRCA1 or BRCA2 mutation; patients with unknown BRCA status who meet NCCN BRCA screening criteria will be screened for BRCA mutation. 2. Histologically or cytologically confirmed HER2-negative metastatic or locally advanced disease that is not amenable to resection or radiation with curative intent. 3. Up to 2 prior cytotoxic regimens for advanced or metastatic breast cancer; patients with no prior cytotoxic regimens for advanced or metastatic disease will only be allowed if they relapsed during or within 12 months of (neo-) adjuvant cytotoxic therapy. 4. Prior therapy should have included a taxane and/or anthracycline (unless contraindication to those) in the neoadjuvant, adjuvant, or advanced/metastatic setting. a. Hormone receptor positive patients must also have hormone resistant disease; either relapsed while on adjuvant endocrine treatment, or within one year of completing adjuvant endocrine treatment, or progression on at least one line of endocrine treatment for advanced cancer. 5. ECOG performance status 0-2 6. Adequate bone marrow, kidney and liver function
Exclusion criteria
1. Patients with platinum resistant cancer 2. Symptomatic uncontrolled brain metastases 3. Prior diagnosis of Stage IV ovarian cancer; Stage III ovarian cancer must have a 5-year disease-free interval; Stage II ovarian cancer must have a 2-year disease-free interval 4. Known hypersensitivity to the components of niraparib 5. Invasive cancer other than breast cancer within 2 years (except basal or squamous cell carcinoma of the skin that has been definitely treated) 6. Pregnant or breast feeding patients 7. Immunocompromised patients 8. Known active Hepatitis B or C 9. Prior treatment with a PARP inhibitor 10. Known history of myelodysplastic syndrome (MDS). 11. known and persistent (\>4 weeks) \>/= grade 3 toxicity or fatigue from prior cancer treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) - Central Review Assessment | From the date of randomization to the date of disease progression or death due to any cause, whichever occurs earlier, up to 4 years | The primary objective of this study is to compare progression-free survival (PFS), as assessed by blinded central review, of participants with advanced/metastatic human epidermal growth factor receptor 2 (HER2)-negative gBRCA mutation breast cancer when treated with niraparib as compared to those treated with physician's choice single agent chemotherapy standards (eribulin, vinorelbine, gemcitabine or capecitabine). PFS is defined as the date of randomization to the date of disease progression or death due to any cause, whichever occurs earlier as per Response evaluation criteria in solid tumors (RECIST) version (v)1.1 as determined by central review assessment. Progressive Disease is defined as at least a 20 percent (%) increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including Baseline) and an absolute increase of \>= 5 millimeter (mm). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE) | Up to 7 years | An adverse event (AE) is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any untoward medical occurrence or effect in a participant, whether or not considered related to the protocol treatment, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing participant hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an medically important event or reaction as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events. |
| Time to Treatment Failure | Date of randomization to discontinuation of treatment for any reason, up to 4 years | Time to treatment failure was defined from the date of randomization to progression or discontinuation of treatment for any reason, including but not restricted to disease progression, treatment toxicity and death. |
| Overall Response Rate (ORR) | Up to 4 years | ORR was defined as the percentage of the participants who achieved a complete response (CR) or partial response (PR) to treatment evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR)=disappearance of all target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures \<10 mm. Partial Response (PR)= at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the Baseline sum of diameters. Percentage values are rounded off up to 1 decimal. |
| Duration of Response (DOR) | Up to 4 years | Duration of response was defined as the time from first documentation of response (confirmed CR or PR) until the time of first documentation of disease progression by RECIST v1.1 or death by any cause. |
| Number of Participants With Serious Adverse Events Related to New Malignancy | Up to 7 years | The number of participants with serious adverse events related to new malignancy were reported. |
| Number of Participants With Subsequent Anticancer Therapies | Up to 7 years | The number of participants with subsequent anticancer therapies were evaluated. Data has been reported as per following categories: any new anitumoral therapy, any chemotherapy, any radiotherapy, any surgery, any hormonal therapy, any targeted agents, and any other treatment. Participants may have received more than one subsequent therapies. |
| Overall Survival | From treatment randomization to date of death of any cause, up to 4 years | Overall Survival (OS) was defined as the time from randomization to the date of death of any causes. |
| Number of Participants With Central BRCA Mutation Status | At Baseline (Cycle 1 Day1) (Cycle duration was 21 days) | Blood samples were collected to evaluate central BRCA mutation status of participants. Baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug. Number of participants with central BRCA mutation status as BRCA1 positive only, BRCA2 positive only, Rearrangement only, BRCA1 and BRCA2 positive, BRCA1 positive and rearrangement, and BRCA2 positive and rearrangement were reported. |
| Progression Free Survival (PFS) - Investigator Assessment | Assessed up to 4 years | PFS is defined as the date of randomization to the date of disease progression or death due to any cause, whichever occurs earlier as per RECIST version 1.1 as determined by Investigator assessment. Progressive Disease is defined as at least a 20 % increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including Baseline) and an absolute increase of \>= 5 mm. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Subsequent Therapies Post Discontinuation of Study Treatment and Association With Potential Survival Related Outcomes | Up to 7 years | The number of participants with any subsequent therapies post-discontinuation of study treatment and association with potential survival related outcomes were planned to be evaluated. |
| Number of Participants With Presence of Genetic and Non-genetic Biomarkers | Up to 7 years | Biomarkers include germline and tumor mutations including somatic BRCA1 and 2 mutations, reversion mutations, loss of heterozygosity as well as genome landscape and transcriptional or functional measures of homologous recombination (HR) deficiency were planned to be evaluated. |
| Number of Participants With Germline BRCA1 and BRCA2 Mutation Status in Association With Survival Related Outcomes | Up to 7 years | Participants with germline BRCA1 and BRCA2 mutation status in association with survival related outcomes were planned to be evaluated. |
| Number of Participants With Minimally Clinically Important Difference (MCID) Status in European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-C30 (EORTC-QLQ-C30) | Up to 7 years | The number of participants with MCID status in EORTC-QLQ-C30 was planned to be evaluated.The EORTC- QLQ-C30 includes 30-items with single and multi-item scales. These include five functional scales (physical functioning, role functioning cognitive functioning, emotional functioning and social functioning), three symptom scales (fatigue, pain and nausea/vomiting), a global health status (GHS)/ Quality-of-Life (QoL) scale, and six single items (constipation, diarrhea, insomnia, dyspnea, appetite loss and financial difficulties). Response options are 1 to 4. The average score can be transformed to 0 to 100, a high score for functional scales/ GHS/QoL represents better functioning ability or health-related quality-of-life (HRQoL), whereas a high score for symptom scales/ single items represents significant symptomatology. |
| Number of Participants With Euroqol 5 Dimension 5 Level (EQ-5D-5L) Dimension Scores by Visit | Up to 7 years | The number of participants with EQ-5D-5L scores by visit were planned to be evaluated. EQ-5D-5L is self-assessment questionnaire, consisting of 5 items covering 5 dimensions (mobility,self care, usual activities, pain/discomfort and anxiety/depression). Each dimension is measured by 5-point Likert scale(no problems, slight problems, moderate problems, severe problems and extreme problems). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Each of these 5 figure health states were to be converted to a single index score. Range for EQ-5D-5L index score is 0 (worst health) to 100 (best health), higher the score better the health status. |
Countries
Belgium, Canada, France, Greece, Hungary, Iceland, Israel, Italy, Netherlands, Poland, Portugal, Spain, United Kingdom, United States
Participant flow
Recruitment details
Previously treated, human epidermal growth factor receptor 2 HER2 negative, germline Breast Cancer gene (gBRCA) mutation positive breast cancer participants were enrolled. The study was terminated due to futility.
Pre-assignment details
Of the 216 participants enrolled, 1 participant was not randomized and 9 participants enrolled based on a local BRCA test results were later determined to be BRCA wild type by central testing. Therefore, only 206 of the 216 participants enrolled were included in the analysis, and were considered in centrally confirmed intent-to-treat (ITT) Population.
Participants by arm
| Arm | Count |
|---|---|
| Physician's Choice Physician selection from 4 standard of care metastatic breast cancer chemotherapies (eribulin or vinorelbine or gemcitabine or capecitabine), until progression or unacceptable toxicity develops. | 71 |
| Niraparib Niraparib 300 milligram (mg) (3x100 mg) capsules once daily until progression or unacceptable toxicity develops. | 135 |
| Total | 206 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Disease Progression | 51 | 110 |
| Overall Study | Not treated | 7 | 3 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Sponsor's decision | 1 | 1 |
| Overall Study | Start of New anti-cancer Treatment | 1 | 0 |
| Overall Study | Toxicity | 1 | 16 |
| Overall Study | Withdrawal by Subject | 10 | 2 |
Baseline characteristics
| Characteristic | Physician's Choice | Niraparib | Total |
|---|---|---|---|
| Age, Customized 18-64 years | 67 Participants | 127 Participants | 194 Participants |
| Age, Customized 65-74 years | 3 Participants | 5 Participants | 8 Participants |
| Age, Customized >=75 years | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 6 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants | 110 Participants | 160 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 15 Participants | 19 Participants | 34 Participants |
| Race/Ethnicity, Customized Race Ashkenazi Jewish descendant | 6 Participants | 5 Participants | 11 Participants |
| Race/Ethnicity, Customized Race Asian | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Black | 3 Participants | 6 Participants | 9 Participants |
| Race/Ethnicity, Customized Race Missing | 2 Participants | 7 Participants | 9 Participants |
| Race/Ethnicity, Customized Race Unknown | 1 Participants | 7 Participants | 8 Participants |
| Race/Ethnicity, Customized Race White or Caucasian | 59 Participants | 108 Participants | 167 Participants |
| Sex: Female, Male Female | 68 Participants | 135 Participants | 203 Participants |
| Sex: Female, Male Male | 3 Participants | 0 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 39 / 65 | 79 / 134 |
| other Total, other adverse events | 62 / 65 | 134 / 134 |
| serious Total, serious adverse events | 4 / 65 | 33 / 134 |
Outcome results
Primary
Progression Free Survival (PFS) - Central Review Assessment
The primary objective of this study is to compare progression-free survival (PFS), as assessed by blinded central review, of participants with advanced/metastatic human epidermal growth factor receptor 2 (HER2)-negative gBRCA mutation breast cancer when treated with niraparib as compared to those treated with physician's choice single agent chemotherapy standards (eribulin, vinorelbine, gemcitabine or capecitabine). PFS is defined as the date of randomization to the date of disease progression or death due to any cause, whichever occurs earlier as per Response evaluation criteria in solid tumors (RECIST) version (v)1.1 as determined by central review assessment. Progressive Disease is defined as at least a 20 percent (%) increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including Baseline) and an absolute increase of \>= 5 millimeter (mm).
Time frame: From the date of randomization to the date of disease progression or death due to any cause, whichever occurs earlier, up to 4 years
Population: Centrally Confirmed intent-to-treat (ITT) Population is defined as all randomized participants with a central confirmation of germline BRCA mutation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Physician's Choice | Progression Free Survival (PFS) - Central Review Assessment | 3.1 Months |
| Niraparib | Progression Free Survival (PFS) - Central Review Assessment | 4.1 Months |
Secondary
Duration of Response (DOR)
Duration of response was defined as the time from first documentation of response (confirmed CR or PR) until the time of first documentation of disease progression by RECIST v1.1 or death by any cause.
Time frame: Up to 4 years
Population: Centrally Confirmed ITT population. Only those participants with confirmed response were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Physician's Choice | Duration of Response (DOR) | 5.65 Months |
| Niraparib | Duration of Response (DOR) | 4.14 Months |
Secondary
Number of Participants With Central BRCA Mutation Status
Blood samples were collected to evaluate central BRCA mutation status of participants. Baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug. Number of participants with central BRCA mutation status as BRCA1 positive only, BRCA2 positive only, Rearrangement only, BRCA1 and BRCA2 positive, BRCA1 positive and rearrangement, and BRCA2 positive and rearrangement were reported.
Time frame: At Baseline (Cycle 1 Day1) (Cycle duration was 21 days)
Population: Centrally Confirmed ITT Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Physician's Choice | Number of Participants With Central BRCA Mutation Status | BRCA2 positive only | 28 Participants |
| Physician's Choice | Number of Participants With Central BRCA Mutation Status | BRCA1 and BRCA2 positive | 1 Participants |
| Physician's Choice | Number of Participants With Central BRCA Mutation Status | BRCA1 positive only | 38 Participants |
| Physician's Choice | Number of Participants With Central BRCA Mutation Status | BRCA1 positive and rearrangement | 1 Participants |
| Physician's Choice | Number of Participants With Central BRCA Mutation Status | Rearrangement only | 3 Participants |
| Physician's Choice | Number of Participants With Central BRCA Mutation Status | BRCA2 positive and rearrangement | 0 Participants |
| Niraparib | Number of Participants With Central BRCA Mutation Status | Rearrangement only | 7 Participants |
| Niraparib | Number of Participants With Central BRCA Mutation Status | BRCA1 positive only | 66 Participants |
| Niraparib | Number of Participants With Central BRCA Mutation Status | BRCA2 positive only | 57 Participants |
| Niraparib | Number of Participants With Central BRCA Mutation Status | BRCA2 positive and rearrangement | 1 Participants |
| Niraparib | Number of Participants With Central BRCA Mutation Status | BRCA1 and BRCA2 positive | 3 Participants |
| Niraparib | Number of Participants With Central BRCA Mutation Status | BRCA1 positive and rearrangement | 1 Participants |
Secondary
Number of Participants With Serious Adverse Events Related to New Malignancy
The number of participants with serious adverse events related to new malignancy were reported.
Time frame: Up to 7 years
Population: Safety Population. Only those participants with data available at specified time were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Physician's Choice | Number of Participants With Serious Adverse Events Related to New Malignancy | 0 Participants |
| Niraparib | Number of Participants With Serious Adverse Events Related to New Malignancy | 2 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE)
An adverse event (AE) is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any untoward medical occurrence or effect in a participant, whether or not considered related to the protocol treatment, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing participant hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an medically important event or reaction as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events.
Time frame: Up to 7 years
Population: Safety Population comprised of all participants who started their allocated treatment (received at least one dose of allocated drug). Only those participants with data available at specified time point were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Physician's Choice | Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE) | SAE | 4 Participants |
| Physician's Choice | Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE) | Non-SAE | 62 Participants |
| Niraparib | Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE) | SAE | 33 Participants |
| Niraparib | Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE) | Non-SAE | 134 Participants |
Secondary
Number of Participants With Subsequent Anticancer Therapies
The number of participants with subsequent anticancer therapies were evaluated. Data has been reported as per following categories: any new anitumoral therapy, any chemotherapy, any radiotherapy, any surgery, any hormonal therapy, any targeted agents, and any other treatment. Participants may have received more than one subsequent therapies.
Time frame: Up to 7 years
Population: Safety Population. Only those participants with data available at specified time were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Physician's Choice | Number of Participants With Subsequent Anticancer Therapies | Any other treatment | 8 Participants |
| Physician's Choice | Number of Participants With Subsequent Anticancer Therapies | Any new antitumoral therapy | 55 Participants |
| Physician's Choice | Number of Participants With Subsequent Anticancer Therapies | Any chemotherapy | 48 Participants |
| Physician's Choice | Number of Participants With Subsequent Anticancer Therapies | Any radiotherapy | 22 Participants |
| Physician's Choice | Number of Participants With Subsequent Anticancer Therapies | Any surgery | 5 Participants |
| Physician's Choice | Number of Participants With Subsequent Anticancer Therapies | Any hormonal therapy | 13 Participants |
| Physician's Choice | Number of Participants With Subsequent Anticancer Therapies | Any targeted agent therapy | 19 Participants |
| Niraparib | Number of Participants With Subsequent Anticancer Therapies | Any other treatment | 17 Participants |
| Niraparib | Number of Participants With Subsequent Anticancer Therapies | Any surgery | 13 Participants |
| Niraparib | Number of Participants With Subsequent Anticancer Therapies | Any new antitumoral therapy | 108 Participants |
| Niraparib | Number of Participants With Subsequent Anticancer Therapies | Any targeted agent therapy | 22 Participants |
| Niraparib | Number of Participants With Subsequent Anticancer Therapies | Any chemotherapy | 96 Participants |
| Niraparib | Number of Participants With Subsequent Anticancer Therapies | Any hormonal therapy | 27 Participants |
| Niraparib | Number of Participants With Subsequent Anticancer Therapies | Any radiotherapy | 48 Participants |
Secondary
Overall Response Rate (ORR)
ORR was defined as the percentage of the participants who achieved a complete response (CR) or partial response (PR) to treatment evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR)=disappearance of all target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures \<10 mm. Partial Response (PR)= at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the Baseline sum of diameters. Percentage values are rounded off up to 1 decimal.
Time frame: Up to 4 years
Population: Centrally Confirmed ITT population. Only those participants with confirmed response were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Physician's Choice | Overall Response Rate (ORR) | 12.5 Percentage of participants |
| Niraparib | Overall Response Rate (ORR) | 21.4 Percentage of participants |
Secondary
Overall Survival
Overall Survival (OS) was defined as the time from randomization to the date of death of any causes.
Time frame: From treatment randomization to date of death of any cause, up to 4 years
Population: Centrally Confirmed ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Physician's Choice | Overall Survival | 15.8 Months |
| Niraparib | Overall Survival | 14.5 Months |
Secondary
Progression Free Survival (PFS) - Investigator Assessment
PFS is defined as the date of randomization to the date of disease progression or death due to any cause, whichever occurs earlier as per RECIST version 1.1 as determined by Investigator assessment. Progressive Disease is defined as at least a 20 % increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including Baseline) and an absolute increase of \>= 5 mm.
Time frame: Assessed up to 4 years
Population: Centrally confirmed ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Physician's Choice | Progression Free Survival (PFS) - Investigator Assessment | 3.1 Months |
| Niraparib | Progression Free Survival (PFS) - Investigator Assessment | 5.0 Months |
Secondary
Time to Treatment Failure
Time to treatment failure was defined from the date of randomization to progression or discontinuation of treatment for any reason, including but not restricted to disease progression, treatment toxicity and death.
Time frame: Date of randomization to discontinuation of treatment for any reason, up to 4 years
Population: Centrally Confirmed ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Physician's Choice | Time to Treatment Failure | 2.6 Months |
| Niraparib | Time to Treatment Failure | 4.3 Months |
Other Pre-specified
Number of Participants With Any Subsequent Therapies Post Discontinuation of Study Treatment and Association With Potential Survival Related Outcomes
The number of participants with any subsequent therapies post-discontinuation of study treatment and association with potential survival related outcomes were planned to be evaluated.
Time frame: Up to 7 years
Population: Safety Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted.
Other Pre-specified
Number of Participants With Euroqol 5 Dimension 5 Level (EQ-5D-5L) Dimension Scores by Visit
The number of participants with EQ-5D-5L scores by visit were planned to be evaluated. EQ-5D-5L is self-assessment questionnaire, consisting of 5 items covering 5 dimensions (mobility,self care, usual activities, pain/discomfort and anxiety/depression). Each dimension is measured by 5-point Likert scale(no problems, slight problems, moderate problems, severe problems and extreme problems). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Each of these 5 figure health states were to be converted to a single index score. Range for EQ-5D-5L index score is 0 (worst health) to 100 (best health), higher the score better the health status.
Time frame: Up to 7 years
Population: ITT Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted.
Other Pre-specified
Number of Participants With Germline BRCA1 and BRCA2 Mutation Status in Association With Survival Related Outcomes
Participants with germline BRCA1 and BRCA2 mutation status in association with survival related outcomes were planned to be evaluated.
Time frame: Up to 7 years
Population: Centrally Confirmed ITT Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted.
Other Pre-specified
Number of Participants With Minimally Clinically Important Difference (MCID) Status in European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-C30 (EORTC-QLQ-C30)
The number of participants with MCID status in EORTC-QLQ-C30 was planned to be evaluated.The EORTC- QLQ-C30 includes 30-items with single and multi-item scales. These include five functional scales (physical functioning, role functioning cognitive functioning, emotional functioning and social functioning), three symptom scales (fatigue, pain and nausea/vomiting), a global health status (GHS)/ Quality-of-Life (QoL) scale, and six single items (constipation, diarrhea, insomnia, dyspnea, appetite loss and financial difficulties). Response options are 1 to 4. The average score can be transformed to 0 to 100, a high score for functional scales/ GHS/QoL represents better functioning ability or health-related quality-of-life (HRQoL), whereas a high score for symptom scales/ single items represents significant symptomatology.
Time frame: Up to 7 years
Population: ITT Population comprised of all randomized participants. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted.
Other Pre-specified
Number of Participants With Presence of Genetic and Non-genetic Biomarkers
Biomarkers include germline and tumor mutations including somatic BRCA1 and 2 mutations, reversion mutations, loss of heterozygosity as well as genome landscape and transcriptional or functional measures of homologous recombination (HR) deficiency were planned to be evaluated.
Time frame: Up to 7 years
Population: Centrally Confirmed ITT Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted.