Ovarian Cancer, Ovarian Neoplasm
Conditions
Keywords
Veliparib, Carboplatin, Paclitaxel, Overall Survival, ABT-888, Randomized, Poly Adenosine Diphosphate (ADP) - Ribose Polymerase (PARP), Ovarian, BRCA, VELIA
Brief summary
The primary objective of the study was to evaluate whether progression-free survival (PFS) was prolonged with the addition of veliparib to standard platinum-based chemotherapy (carboplatin/paclitaxel \[C/P\]) and continued as maintenance therapy compared with chemotherapy alone.
Detailed description
Participants were randomized in a 1:1:1 ratio to one of three arms. Randomization in the entire population was stratified according to the timing of surgery and residual disease status (any residual disease after primary surgery vs. no residual disease after primary surgery vs. interval surgery) and the paclitaxel schedule (weekly vs. every 3 -weeks), stage of disease (III vs. IV), geographic region (Japan vs. North America and rest of world \[ROW\]), and germline breast cancer susceptibility gene (BRCA) mutation status (positive versus negative or Unknown). Cytoreductive surgery could be performed before randomization and the initiation of study treatment (primary) or after 3 cycles of study treatment (interval). The weekly or every-3-week paclitaxel schedule and the choice of primary or interval cytoreductive surgery were determined at the discretion of the investigator. The primary objective was evaluated in the BRCA-deficient cohort, participants with homologous recombination deficiency (HRD), and the intention-to-treat (ITT) population. These populations were sequentially inclusive, with the HRD population including the BRCA-deficient population, and the ITT population including the HRD and BRCA-deficient populations. The BRCA-deficient population was defined as participants with either a germline (gBRCA) and/or tissue-based (tBRCA) deleterious or suspected deleterious mutation in BRCA1 or BRCA2 confirmed by centralized testing. The HRD population was defined as participants with HRD tumors based on HRD score or presence of a deleterious or suspected deleterious mutation in BRCA1 or BRCA2 as determined by centralized testing.
Interventions
DRUGVeliparib
Capsules for oral administration
DRUGPaclitaxel
Administered by intravenous infusion, either 80 mg/m² of body-surface area (BSA) on Days 1, 8, and 15 of each 21-day cycle (weekly dosing), or 175 mg/m² of BSA on Day 1 of each 21-day cycle (3-week dosing).
DRUGCarboplatin
Administered by intravenous infusion at an area under the curve (AUC) of 6 mg/mL/min every 3 weeks.
OTHERPlacebo to Veliparib
Capsules for oral administration
Sponsors
Australia New Zealand Gynaecological Oncology Group
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologic diagnosis of International Federation of Gynecology and Obstetrics (FIGO) Stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, with the appropriate tissue available for histologic evaluation. 2. High-grade serous adenocarcinoma 3. Willing to undergo testing for gBRCA. 4. Adequate hematologic, renal, and hepatic function. 5. Neuropathy (sensory and motor) less than or equal to Grade 1. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. 7. Participants who undergo primary cytoreductive surgery must be entered between 1 and 12 weeks after surgery. Participants undergoing interval surgery must have a tumor sample confirming the histological diagnosis prior to enrollment. 8. Participants with measurable disease or non-measurable disease are eligible. Participants may or may not have cancer-related symptoms. 9. Participant has one of the following available for pharmacodynamic analyses including somatic BRCA testing: Archived diagnostic formalin-fixed paraffin embedded (FFPE) tumor tissue; or tumor tissue biopsy collected prior to Cycle 1 Day 1.
Exclusion criteria
1. Endometrioid adenocarcinoma, carcinosarcoma, undifferentiated carcinoma, mixed epithelial adenocarcinoma, adenocarcinoma not otherwise specified, mucinous adenocarcinoma, clear cell adenocarcinoma, low-grade serous adenocarcinoma, or malignant Brenner's tumor. 2. Participants with synchronous primary endometrial cancer, or a past history of endometrial cancer unless all of the following conditions are met: endometrial cancer stage not greater than IA, no vascular or lymphatic invasion, no poorly differentiated subtypes including serous, clear cell, or other FIGO grade 3 lesions. 3. Participants with any evidence of other invasive malignancy being present within the last 3 years (with the exception of non-melanoma skin cancer). Participants are also excluded if their previous cancer treatment contraindicates this protocol's therapy. 4. Received prior radiotherapy to any portion of the abdominal cavity or pelvis. 5. Received prior chemotherapy for any abdominal or pelvic tumor. 6. Clinically significant uncontrolled condition(s). 7. Known history of allergic reaction to Cremophor-paclitaxel, carboplatin, Azo-Colourant Tartrazine (also known as FD&C Yellow 5 or E102), Azo-Colourant Orange Yellow-S (also known as FD&C Yellow 6 or E110) or known contraindications to any study supplied drug. 8. History or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) within 6 months of Cycle 1 Day 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) in the BRCA-deficient Population (Arm 3 vs Arm 1) | From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months. | PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death if disease progression was not reached. If the participant did not have an event of disease progression or death prior to the analysis cut-off date, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. The analysis of PFS occurred when the protocol-specified number of PFS events was reached. Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions. |
| Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort (Arm 3 vs Arm 1) | From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months. | PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death if disease progression was not reached. If the participant did not have an event of disease progression or death, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. The primary analysis of PFS occurred when the protocol-specified number of PFS events was reached and was performed in 3 sequentially inclusive populations. Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions. . |
| Progression-Free Survival (PFS) in the Intention-to-treat Population (Arm 3 vs Arm 1) | From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months. | PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death (all causes of mortality) if disease progression was not reached. If the participant did not have an event of disease progression according to RECIST criteria (as or death, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions. The primary analysis of PFS occurred when the protocol-specified number of PFS events was reached. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in the BRCA-deficient Population | From the time of randomization to the end of the study, up to 98 months | OS is defined as the time from the day the participant was randomized to the date of death, and was calculated using Kaplan-Meier methods. All events of death will be included, regardless of whether the event occurs while the participant is still taking study drug, or after discontinuation of study drug. If a participant has not died, then the data will be censored at the date the participant is last known to be alive. |
| Overall Survival (OS) in the Homologous Recombination Deficiency Population | From the time of randomization to the end of the study, up to 98 months | OS is defined as the time from the day the participant was randomized to the date of death, and was calculated using Kaplan-Meier methods. All events of death will be included, regardless of whether the event occurs while the participant is still taking study drug, or after discontinuation of study drug. If a participant has not died, then the data will be censored at the date the participant is last known to be alive. |
| Overall Survival (OS) in the Whole Population | From the time of randomization to the end of the study, up to 98 months | OS is defined as the time from the day the participant was randomized to the date of death, and was calculated using Kaplan-Meier methods. All events of death will be included, regardless of whether the event occurs while the participant is still taking study drug, or after discontinuation of study drug. If a participant has not died, then the data will be censored at the date the participant is last known to be alive. |
| Progression-Free Survival (PFS) in the BRCA-deficient Population (Arm 2 vs Arm 1) | From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months. | PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death if disease progression was not reached. If the participant did not have an event of disease progression or death prior to the analysis cut-off date, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. The analysis of PFS occurred when the protocol-specified number of PFS events was reached. Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions. |
| Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Baseline and Day 1 of Cycles 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35 | The Disease Related Symptom score is a subset of the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 (NFOSI-18), which evaluates nine symptoms related to ovarian cancer. The NFOSI-18 DRS score ranges from 0 to 36, with higher scores indicating a lower burden of symptoms and a score of 0 being severely symptomatic. A 3-point difference was defined as clinically meaningful. A positive change from Baseline indicates improvement. Change from Baseline was calculated using a used a mixed-model for repeated measures (MMRM) with treatment, stratification factors of residual disease and stage of disease, time point and treatment-by-time point interaction as fixed effect factors, and Baseline DRS score as a covariate. DRS was not included in the fixed-sequence testing procedure. |
| Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Baseline and Day 1 of Cycles 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35 | The Disease Related Symptom score is a subset of the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 (NFOSI-18), which evaluates nine symptoms related to ovarian cancer. The NFOSI-18 DRS score ranges from 0 to 36, with higher scores indicating a lower burden of symptoms and a score of 0 being severely symptomatic. A 3-point difference was defined as clinically meaningful. A positive change from Baseline indicates improvement. Change from Baseline was calculated using a used a mixed-model for repeated measures (MMRM) with treatment, stratification factors of residual disease, stage of disease, choice of paclitaxel dosing regimen and BRCA-deficient status, time point and treatment-by-time point interaction as fixed effect factors, and Baseline DRS score as a covariate. DRS was not included in the fixed-sequence testing procedure. |
| Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Baseline and Day 1 of Cycles 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35 | The Disease Related Symptom score is a subset of the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 (NFOSI-18), which evaluates nine symptoms related to ovarian cancer. The NFOSI-18 DRS score ranges from 0 to 36, with higher scores indicating a lower burden of symptoms and a score of 0 being severely symptomatic. A 3-point difference was defined as clinically meaningful. A positive change from Baseline indicates improvement. Change from Baseline was calculated using a used a mixed-model for repeated measures (MMRM) with treatment, stratification factors of residual disease and stage of disease, time point and treatment-by-time point interaction as fixed effect factors, and Baseline DRS score as a covariate. DRS was not included in the fixed-sequence testing procedure. |
| Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort (Arm 2 vs Arm 1) | From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months. | PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death if disease progression was not reached. If the participant did not have an event of disease progression or death, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. The primary analysis of PFS occurred when the protocol-specified number of PFS events was reached and was performed in 3 sequentially inclusive populations. Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions. . |
| Progression-Free Survival (PFS) in the Intention-to-treat Population (Arm 2 vs Arm 1) | From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months. | PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death (all causes of mortality) if disease progression was not reached. If the participant did not have an event of disease progression according to RECIST criteria (as or death, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions. The primary analysis of PFS occurred when the protocol-specified number of PFS events was reached. |
Countries
Australia, Brazil, Denmark, Israel, Japan, New Zealand, Poland, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
This trial was conducted at 188 sites in 10 countries (Australia, Brazil, Denmark, Israel, Japan, Poland, Republic of Korea, Spain, United Kingdom, and United States).
Pre-assignment details
Participants were randomized in a 1:1:1 ratio to one of three treatment groups. Randomization was stratified according to the timing of surgery and residual disease after primary surgery or interval surgery, the paclitaxel schedule, stage of disease, geographic region, and germline breast cancer susceptibility gene (BRCA) mutation status.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + Carboplatin + Paclitaxel -> Placebo Participants received placebo to veliparib orally twice a day in combination with carboplatin given at an area under the curve \[AUC\] of 6 mg per milliliter per minute (mg/mL/min), every 3 weeks, and paclitaxel 175 mg per square meter (mg/m²) of body-surface area (BSA), administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.
Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy. | 375 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks, and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.
Participants who completed chemotherapy without disease progression received matching placebo twice daily for an additional thirty 21-day cycles of maintenance therapy. | 383 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib Participants received 150 mg veliparib orally twice a day in combination with carboplatin given at an AUC of 6 mg/mL/min every 3 weeks, and paclitaxel 175 mg/m² of BSA administered every 3 weeks, or 80 mg/m² administered weekly, for six 21-day cycles.
Participants who completed chemotherapy without disease progression received single-agent veliparib at a dose of 300 mg twice daily for 2 weeks (transition period) and then 400 mg veliparib twice daily if the dose in the transition period was not associated with limiting side effects for an additional thirty 21-day cycles of maintenance therapy. | 382 |
| Total | 1,140 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 224 | 227 | 199 |
| Overall Study | Lost to Follow-up | 8 | 15 | 13 |
| Overall Study | Missing due to site non-compliance | 0 | 2 | 3 |
| Overall Study | Other, not specified | 5 | 7 | 14 |
| Overall Study | Sponsor discontinued study | 117 | 110 | 122 |
| Overall Study | Withdrew consent | 21 | 22 | 31 |
Baseline characteristics
| Characteristic | Placebo + Carboplatin + Paclitaxel -> Placebo | Veliparib + Carboplatin + Paclitaxel -> Placebo | Veliparib + Carboplatin + Paclitaxel -> Veliparib | Total |
|---|---|---|---|---|
| Age, Continuous | 62.0 years | 62.0 years | 62.0 years | 62.0 years |
| Age, Customized < 65 years | 233 Participants | 226 Participants | 228 Participants | 687 Participants |
| Age, Customized ≥ 65 years | 142 Participants | 157 Participants | 154 Participants | 453 Participants |
| BRCA-Deficient Status Germline or tissue BRCA1/2 mutation | 92 Participants | 98 Participants | 108 Participants | 298 Participants |
| BRCA-Deficient Status Germline or tissue BRCA1/2 wildtype | 254 Participants | 243 Participants | 245 Participants | 742 Participants |
| BRCA-Deficient Status Missing | 29 Participants | 42 Participants | 29 Participants | 100 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 28 Participants | 27 Participants | 26 Participants | 81 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 347 Participants | 356 Participants | 356 Participants | 1059 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Geographic Region Japan | 23 Participants | 30 Participants | 25 Participants | 78 Participants |
| Geographic Region North America | 266 Participants | 261 Participants | 267 Participants | 794 Participants |
| Geographic Region Rest of World | 86 Participants | 92 Participants | 90 Participants | 268 Participants |
| Germline BRCA Status Germline BRCA1/2 mutation | 63 Participants | 71 Participants | 80 Participants | 214 Participants |
| Germline BRCA Status Germline BRCA1/2 wildtype | 305 Participants | 305 Participants | 298 Participants | 908 Participants |
| Germline BRCA Status Missing | 7 Participants | 7 Participants | 4 Participants | 18 Participants |
| Homologous Recombination Deficiency (HRD) Status HRD | 207 Participants | 206 Participants | 214 Participants | 627 Participants |
| Homologous Recombination Deficiency (HRD) Status Missing | 44 Participants | 54 Participants | 43 Participants | 141 Participants |
| Homologous Recombination Deficiency (HRD) Status Non-HRD | 124 Participants | 123 Participants | 125 Participants | 372 Participants |
| Paclitaxel Dosing Regimen Every 3 weeks | 179 Participants | 178 Participants | 189 Participants | 546 Participants |
| Paclitaxel Dosing Regimen Missing | 3 Participants | 2 Participants | 3 Participants | 8 Participants |
| Paclitaxel Dosing Regimen Weekly | 193 Participants | 203 Participants | 190 Participants | 586 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 59 Participants | 69 Participants | 56 Participants | 184 Participants |
| Race/Ethnicity, Customized Black or African American | 10 Participants | 13 Participants | 20 Participants | 43 Participants |
| Race/Ethnicity, Customized Missing | 2 Participants | 3 Participants | 3 Participants | 8 Participants |
| Race/Ethnicity, Customized Multi-race | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 299 Participants | 297 Participants | 300 Participants | 896 Participants |
| Residual Disease After Interval Surgery Any macroscopic residual disease | 31 Participants | 34 Participants | 27 Participants | 92 Participants |
| Residual Disease After Interval Surgery Microscopic residual disease only | 22 Participants | 30 Participants | 24 Participants | 76 Participants |
| Residual Disease After Interval Surgery Missing | 4 Participants | 4 Participants | 3 Participants | 11 Participants |
| Residual Disease After Interval Surgery No residual disease | 50 Participants | 46 Participants | 45 Participants | 141 Participants |
| Residual Disease After Primary Surgery Any macroscopic residual disease | 76 Participants | 89 Participants | 83 Participants | 248 Participants |
| Residual Disease After Primary Surgery Microscopic residual disease only | 58 Participants | 46 Participants | 54 Participants | 158 Participants |
| Residual Disease After Primary Surgery No residual disease | 116 Participants | 118 Participants | 124 Participants | 358 Participants |
| Sex: Female, Male Female | 375 Participants | 383 Participants | 382 Participants | 1140 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Stage of Disease Missing | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Stage of Disease Stage III | 292 Participants | 288 Participants | 295 Participants | 875 Participants |
| Stage of Disease Stage IV | 82 Participants | 94 Participants | 87 Participants | 263 Participants |
| Type of Surgery Received Interval | 107 Participants | 114 Participants | 99 Participants | 320 Participants |
| Type of Surgery Received No surgery received | 18 Participants | 16 Participants | 22 Participants | 56 Participants |
| Type of Surgery Received Primary | 250 Participants | 253 Participants | 261 Participants | 764 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 228 / 375 | 234 / 383 | 209 / 382 |
| other Total, other adverse events | 369 / 375 | 375 / 383 | 376 / 382 |
| serious Total, serious adverse events | 143 / 375 | 130 / 383 | 146 / 382 |
Outcome results
Primary
Progression-Free Survival (PFS) in the BRCA-deficient Population (Arm 3 vs Arm 1)
PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death if disease progression was not reached. If the participant did not have an event of disease progression or death prior to the analysis cut-off date, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. The analysis of PFS occurred when the protocol-specified number of PFS events was reached. Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions.
Time frame: From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.
Population: Analyses were performed in 3 sequentially inclusive populations. The first analysis was conducted using the BRCA-mutation cohort which included participants with either a gBRCA and/or tBRCA deleterious or suspected deleterious mutation in BRCA1 or BRCA2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Carboplatin + Paclitaxel -> Placebo | Progression-Free Survival (PFS) in the BRCA-deficient Population (Arm 3 vs Arm 1) | 22.0 months |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Progression-Free Survival (PFS) in the BRCA-deficient Population (Arm 3 vs Arm 1) | 21.1 months |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Progression-Free Survival (PFS) in the BRCA-deficient Population (Arm 3 vs Arm 1) | 34.7 months |
Comparison: The primary efficacy analyses compared investigator-assessed PFS in the Veliparib + Carboplatin + Paclitaxel -\> Veliparib group (Arm 3) vs. the Placebo + Carboplatin + Paclitaxel -\> Placebo group (Arm 1).p-value: <0.00195% CI: [0.277, 0.683]Log Rank
Primary
Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort (Arm 3 vs Arm 1)
PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death if disease progression was not reached. If the participant did not have an event of disease progression or death, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. The primary analysis of PFS occurred when the protocol-specified number of PFS events was reached and was performed in 3 sequentially inclusive populations. Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions. .
Time frame: From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.
Population: Analyses were performed in 3 sequentially inclusive populations. The second analysis was conducted using the HRD cohort which included participants in the BRCA-mutation cohort and those determined to have HRD tumors.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Carboplatin + Paclitaxel -> Placebo | Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort (Arm 3 vs Arm 1) | 20.5 months |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort (Arm 3 vs Arm 1) | 18.1 months |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort (Arm 3 vs Arm 1) | 31.9 months |
Comparison: The primary efficacy analyses compared investigator-assessed PFS in the Veliparib + Carboplatin + Paclitaxel -\> Veliparib group (Arm 3) vs. the Placebo + Carboplatin + Paclitaxel -\> Placebo group (Arm 1).p-value: <0.00195% CI: [0.433, 0.756]Log Rank
Primary
Progression-Free Survival (PFS) in the Intention-to-treat Population (Arm 3 vs Arm 1)
PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death (all causes of mortality) if disease progression was not reached. If the participant did not have an event of disease progression according to RECIST criteria (as or death, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions. The primary analysis of PFS occurred when the protocol-specified number of PFS events was reached.
Time frame: From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.
Population: Analyses were performed in 3 sequentially inclusive populations. The third analysis was conducted using the intention-to-treat (ITT) population (all randomized participants).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Carboplatin + Paclitaxel -> Placebo | Progression-Free Survival (PFS) in the Intention-to-treat Population (Arm 3 vs Arm 1) | 17.3 months |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Progression-Free Survival (PFS) in the Intention-to-treat Population (Arm 3 vs Arm 1) | 15.2 months |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Progression-Free Survival (PFS) in the Intention-to-treat Population (Arm 3 vs Arm 1) | 23.5 months |
Comparison: The primary efficacy analyses compared investigator-assessed PFS in the Veliparib + Carboplatin + Paclitaxel -\> Veliparib group (Arm 3) vs. the Placebo + Carboplatin + Paclitaxel -\> Placebo group (Arm 1).p-value: <0.00195% CI: [0.562, 0.831]Log Rank
Secondary
Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population
The Disease Related Symptom score is a subset of the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 (NFOSI-18), which evaluates nine symptoms related to ovarian cancer. The NFOSI-18 DRS score ranges from 0 to 36, with higher scores indicating a lower burden of symptoms and a score of 0 being severely symptomatic. A 3-point difference was defined as clinically meaningful. A positive change from Baseline indicates improvement. Change from Baseline was calculated using a used a mixed-model for repeated measures (MMRM) with treatment, stratification factors of residual disease and stage of disease, time point and treatment-by-time point interaction as fixed effect factors, and Baseline DRS score as a covariate. DRS was not included in the fixed-sequence testing procedure.
Time frame: Baseline and Day 1 of Cycles 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35
Population: BRCA-mutation population, participants with available data at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 33 | 3.9 score on a scale | Standard Error 0.66 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 25 | 4.0 score on a scale | Standard Error 0.58 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 15 | 4.3 score on a scale | Standard Error 0.53 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 7 | 2.6 score on a scale | Standard Error 0.55 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 23 | 4.2 score on a scale | Standard Error 0.55 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 17 | 3.8 score on a scale | Standard Error 0.56 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 35 | 4.5 score on a scale | Standard Error 0.61 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 21 | 4.6 score on a scale | Standard Error 0.59 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 19 | 4.0 score on a scale | Standard Error 0.62 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 31 | 4.8 score on a scale | Standard Error 0.57 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 9 | 3.3 score on a scale | Standard Error 0.6 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 5 | 1.7 score on a scale | Standard Error 0.57 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 29 | 4.0 score on a scale | Standard Error 0.66 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 11 | 3.2 score on a scale | Standard Error 0.56 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 3 | 1.8 score on a scale | Standard Error 0.52 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 27 | 4.5 score on a scale | Standard Error 0.56 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 13 | 3.6 score on a scale | Standard Error 0.57 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 27 | 4.8 score on a scale | Standard Error 0.56 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 3 | 0.5 score on a scale | Standard Error 0.53 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 5 | 0.7 score on a scale | Standard Error 0.58 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 7 | 1.8 score on a scale | Standard Error 0.54 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 9 | 3.3 score on a scale | Standard Error 0.6 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 11 | 3.6 score on a scale | Standard Error 0.55 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 13 | 3.8 score on a scale | Standard Error 0.57 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 15 | 4.0 score on a scale | Standard Error 0.54 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 17 | 4.0 score on a scale | Standard Error 0.57 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 19 | 4.0 score on a scale | Standard Error 0.63 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 21 | 3.9 score on a scale | Standard Error 0.59 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 23 | 4.0 score on a scale | Standard Error 0.56 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 25 | 5.0 score on a scale | Standard Error 0.6 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 33 | 5.1 score on a scale | Standard Error 0.67 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 29 | 5.3 score on a scale | Standard Error 0.66 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 31 | 4.8 score on a scale | Standard Error 0.58 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 35 | 5.0 score on a scale | Standard Error 0.62 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 13 | 3.0 score on a scale | Standard Error 0.57 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 5 | 0.3 score on a scale | Standard Error 0.56 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 25 | 3.5 score on a scale | Standard Error 0.55 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 11 | 2.9 score on a scale | Standard Error 0.54 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 33 | 3.9 score on a scale | Standard Error 0.59 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 27 | 3.0 score on a scale | Standard Error 0.52 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 9 | 2.4 score on a scale | Standard Error 0.59 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 3 | 0.9 score on a scale | Standard Error 0.51 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 29 | 2.9 score on a scale | Standard Error 0.59 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 7 | 1.8 score on a scale | Standard Error 0.54 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 19 | 2.7 score on a scale | Standard Error 0.59 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 17 | 3.2 score on a scale | Standard Error 0.55 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 35 | 3.2 score on a scale | Standard Error 0.56 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 21 | 3.2 score on a scale | Standard Error 0.55 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 15 | 3.4 score on a scale | Standard Error 0.52 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 31 | 2.9 score on a scale | Standard Error 0.52 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population | Cycle 23 | 2.8 score on a scale | Standard Error 0.52 |
Secondary
Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population
The Disease Related Symptom score is a subset of the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 (NFOSI-18), which evaluates nine symptoms related to ovarian cancer. The NFOSI-18 DRS score ranges from 0 to 36, with higher scores indicating a lower burden of symptoms and a score of 0 being severely symptomatic. A 3-point difference was defined as clinically meaningful. A positive change from Baseline indicates improvement. Change from Baseline was calculated using a used a mixed-model for repeated measures (MMRM) with treatment, stratification factors of residual disease and stage of disease, time point and treatment-by-time point interaction as fixed effect factors, and Baseline DRS score as a covariate. DRS was not included in the fixed-sequence testing procedure.
Time frame: Baseline and Day 1 of Cycles 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35
Population: HRD population, participants with available data at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 9 | 3.3 score on a scale | Standard Error 0.37 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 33 | 4.2 score on a scale | Standard Error 0.45 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 23 | 4.1 score on a scale | Standard Error 0.38 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 21 | 4.6 score on a scale | Standard Error 0.4 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 35 | 4.1 score on a scale | Standard Error 0.44 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 15 | 4.2 score on a scale | Standard Error 0.35 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 7 | 2.4 score on a scale | Standard Error 0.35 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 3 | 1.5 score on a scale | Standard Error 0.35 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 27 | 4.4 score on a scale | Standard Error 0.39 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 5 | 1.7 score on a scale | Standard Error 0.37 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 19 | 4.2 score on a scale | Standard Error 0.4 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 13 | 3.6 score on a scale | Standard Error 0.37 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 29 | 4.2 score on a scale | Standard Error 0.43 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 17 | 3.9 score on a scale | Standard Error 0.39 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 11 | 3.5 score on a scale | Standard Error 0.36 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 31 | 3.9 score on a scale | Standard Error 0.41 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 25 | 4.1 score on a scale | Standard Error 0.4 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 7 | 1.8 score on a scale | Standard Error 0.36 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 21 | 3.6 score on a scale | Standard Error 0.41 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 23 | 3.6 score on a scale | Standard Error 0.39 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 25 | 4.4 score on a scale | Standard Error 0.41 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 27 | 4.4 score on a scale | Standard Error 0.4 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 29 | 4.7 score on a scale | Standard Error 0.44 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 31 | 4.3 score on a scale | Standard Error 0.42 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 33 | 4.7 score on a scale | Standard Error 0.45 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 35 | 4.6 score on a scale | Standard Error 0.45 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 3 | 0.5 score on a scale | Standard Error 0.36 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 5 | 1.1 score on a scale | Standard Error 0.37 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 9 | 3.6 score on a scale | Standard Error 0.38 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 11 | 3.5 score on a scale | Standard Error 0.36 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 13 | 3.8 score on a scale | Standard Error 0.38 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 15 | 3.9 score on a scale | Standard Error 0.36 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 17 | 3.4 score on a scale | Standard Error 0.4 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 19 | 3.7 score on a scale | Standard Error 0.42 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 23 | 3.1 score on a scale | Standard Error 0.38 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 9 | 2.3 score on a scale | Standard Error 0.38 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 29 | 3.2 score on a scale | Standard Error 0.41 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 19 | 2.7 score on a scale | Standard Error 0.41 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 11 | 2.7 score on a scale | Standard Error 0.36 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 27 | 3.0 score on a scale | Standard Error 0.38 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 17 | 3.0 score on a scale | Standard Error 0.4 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 13 | 2.7 score on a scale | Standard Error 0.39 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 25 | 3.5 score on a scale | Standard Error 0.4 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 21 | 3.0 score on a scale | Standard Error 0.4 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 3 | 0.9 score on a scale | Standard Error 0.35 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 15 | 3.3 score on a scale | Standard Error 0.37 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 5 | 0.8 score on a scale | Standard Error 0.37 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 35 | 3.4 score on a scale | Standard Error 0.43 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 33 | 3.9 score on a scale | Standard Error 0.42 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 7 | 2.2 score on a scale | Standard Error 0.35 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population | Cycle 31 | 3.3 score on a scale | Standard Error 0.4 |
Secondary
Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population
The Disease Related Symptom score is a subset of the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 (NFOSI-18), which evaluates nine symptoms related to ovarian cancer. The NFOSI-18 DRS score ranges from 0 to 36, with higher scores indicating a lower burden of symptoms and a score of 0 being severely symptomatic. A 3-point difference was defined as clinically meaningful. A positive change from Baseline indicates improvement. Change from Baseline was calculated using a used a mixed-model for repeated measures (MMRM) with treatment, stratification factors of residual disease, stage of disease, choice of paclitaxel dosing regimen and BRCA-deficient status, time point and treatment-by-time point interaction as fixed effect factors, and Baseline DRS score as a covariate. DRS was not included in the fixed-sequence testing procedure.
Time frame: Baseline and Day 1 of Cycles 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35
Population: All randomized participants with available data at each time point
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 13 | 3.8 score on a scale | Standard Error 0.3 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 35 | 4.4 score on a scale | Standard Error 0.37 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 21 | 4.3 score on a scale | Standard Error 0.34 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 15 | 4.2 score on a scale | Standard Error 0.3 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 33 | 4.1 score on a scale | Standard Error 0.38 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 19 | 4.4 score on a scale | Standard Error 0.32 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 17 | 4.1 score on a scale | Standard Error 0.32 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 31 | 4.0 score on a scale | Standard Error 0.36 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 7 | 2.3 score on a scale | Standard Error 0.29 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 3 | 1.5 score on a scale | Standard Error 0.28 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 29 | 4.4 score on a scale | Standard Error 0.34 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 9 | 3.3 score on a scale | Standard Error 0.29 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 5 | 1.6 score on a scale | Standard Error 0.29 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 27 | 4.4 score on a scale | Standard Error 0.33 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 11 | 3.5 score on a scale | Standard Error 0.29 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 25 | 4.0 score on a scale | Standard Error 0.34 |
| Placebo + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 23 | 4.0 score on a scale | Standard Error 0.33 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 9 | 3.8 score on a scale | Standard Error 0.29 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 3 | 0.4 score on a scale | Standard Error 0.28 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 5 | 0.9 score on a scale | Standard Error 0.29 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 7 | 1.8 score on a scale | Standard Error 0.29 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 11 | 4.0 score on a scale | Standard Error 0.28 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 13 | 4.0 score on a scale | Standard Error 0.3 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 15 | 3.8 score on a scale | Standard Error 0.3 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 17 | 3.7 score on a scale | Standard Error 0.32 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 19 | 4.0 score on a scale | Standard Error 0.32 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 21 | 3.6 score on a scale | Standard Error 0.34 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 23 | 3.9 score on a scale | Standard Error 0.33 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 25 | 4.1 score on a scale | Standard Error 0.35 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 27 | 4.2 score on a scale | Standard Error 0.34 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 29 | 4.4 score on a scale | Standard Error 0.35 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 31 | 4.2 score on a scale | Standard Error 0.37 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 33 | 4.4 score on a scale | Standard Error 0.38 |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 35 | 4.2 score on a scale | Standard Error 0.37 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 23 | 3.3 score on a scale | Standard Error 0.32 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 31 | 3.3 score on a scale | Standard Error 0.35 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 25 | 3.5 score on a scale | Standard Error 0.33 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 9 | 2.4 score on a scale | Standard Error 0.29 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 35 | 3.7 score on a scale | Standard Error 0.35 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 27 | 3.5 score on a scale | Standard Error 0.32 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 7 | 2.1 score on a scale | Standard Error 0.29 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 33 | 3.7 score on a scale | Standard Error 0.36 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 17 | 3.4 score on a scale | Standard Error 0.32 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 15 | 3.3 score on a scale | Standard Error 0.3 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 29 | 3.4 score on a scale | Standard Error 0.33 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 19 | 3.1 score on a scale | Standard Error 0.32 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 13 | 3.2 score on a scale | Standard Error 0.3 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 5 | 0.8 score on a scale | Standard Error 0.29 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 21 | 3.3 score on a scale | Standard Error 0.33 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 11 | 3.0 score on a scale | Standard Error 0.29 |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Change From Baseline in Disease Related Symptom (DRS) Score in the Whole Population | Cycle 3 | 0.9 score on a scale | Standard Error 0.28 |
Secondary
Overall Survival (OS) in the BRCA-deficient Population
OS is defined as the time from the day the participant was randomized to the date of death, and was calculated using Kaplan-Meier methods. All events of death will be included, regardless of whether the event occurs while the participant is still taking study drug, or after discontinuation of study drug. If a participant has not died, then the data will be censored at the date the participant is last known to be alive.
Time frame: From the time of randomization to the end of the study, up to 98 months
Population: BRCA-Deficient population: All randomized participants with germline and/or tissue deleterious/suspected deleterious BRCA1/2 mutation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Carboplatin + Paclitaxel -> Placebo | Overall Survival (OS) in the BRCA-deficient Population | 89.5 months |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Overall Survival (OS) in the BRCA-deficient Population | NA months |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Overall Survival (OS) in the BRCA-deficient Population | NA months |
Comparison: Veliparib + Carboplatin + Paclitaxel -\> Veliparib (Arm 3) versus Placebo + Carboplatin + Paclitaxel -\> Placebo (Arm 1)p-value: 0.32895% CI: [0.567, 1.429]Log Rank
Comparison: Veliparib + Carboplatin + Paclitaxel -\> Placebo (Arm 2) versus Placebo + Carboplatin + Paclitaxel -\> Placebo (Arm 1)p-value: 0.80895% CI: [0.78, 1.903]Log Rank
Secondary
Overall Survival (OS) in the Homologous Recombination Deficiency Population
OS is defined as the time from the day the participant was randomized to the date of death, and was calculated using Kaplan-Meier methods. All events of death will be included, regardless of whether the event occurs while the participant is still taking study drug, or after discontinuation of study drug. If a participant has not died, then the data will be censored at the date the participant is last known to be alive.
Time frame: From the time of randomization to the end of the study, up to 98 months
Population: All randomized participants considered BRCA-Deficient and those determined to have HRD tumors based on HRD score
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Carboplatin + Paclitaxel -> Placebo | Overall Survival (OS) in the Homologous Recombination Deficiency Population | 71.5 months |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Overall Survival (OS) in the Homologous Recombination Deficiency Population | 74.4 months |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Overall Survival (OS) in the Homologous Recombination Deficiency Population | NA months |
Comparison: Veliparib + Carboplatin + Paclitaxel -\> Veliparib (Arm 3) versus Placebo + Carboplatin + Paclitaxel -\> Placebo (Arm 1)p-value: 0.11695% CI: [0.64, 1.114]Log Rank
Comparison: Veliparib + Carboplatin + Paclitaxel -\> Placebo (Arm 2) versus Placebo + Carboplatin + Paclitaxel -\> Placebo (Arm 1)p-value: 0.35295% CI: [0.726, 1.242]Log Rank
Secondary
Overall Survival (OS) in the Whole Population
OS is defined as the time from the day the participant was randomized to the date of death, and was calculated using Kaplan-Meier methods. All events of death will be included, regardless of whether the event occurs while the participant is still taking study drug, or after discontinuation of study drug. If a participant has not died, then the data will be censored at the date the participant is last known to be alive.
Time frame: From the time of randomization to the end of the study, up to 98 months
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Carboplatin + Paclitaxel -> Placebo | Overall Survival (OS) in the Whole Population | 57.8 months |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Overall Survival (OS) in the Whole Population | 58.0 months |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Overall Survival (OS) in the Whole Population | 59.2 months |
Comparison: Veliparib + Carboplatin + Paclitaxel -\> Veliparib (Arm 3) versus Placebo + Carboplatin + Paclitaxel -\> Placebo (Arm 1)p-value: 0.28395% CI: [0.782, 1.144]Log Rank
Comparison: Veliparib + Carboplatin + Paclitaxel -\> Placebo (Arm 2) versus Placebo + Carboplatin + Paclitaxel -\> Placebo (Arm 1)p-value: 0.63895% CI: [0.859, 1.244]Log Rank
Secondary
Progression-Free Survival (PFS) in the BRCA-deficient Population (Arm 2 vs Arm 1)
PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death if disease progression was not reached. If the participant did not have an event of disease progression or death prior to the analysis cut-off date, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. The analysis of PFS occurred when the protocol-specified number of PFS events was reached. Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions.
Time frame: From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.
Population: Analyses were performed in 3 sequentially inclusive populations. The first analysis was conducted using the BRCA-mutation cohort which included participants with either a gBRCA and/or tBRCA deleterious or suspected deleterious mutation in BRCA1 or BRCA2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Carboplatin + Paclitaxel -> Placebo | Progression-Free Survival (PFS) in the BRCA-deficient Population (Arm 2 vs Arm 1) | 22.0 months |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Progression-Free Survival (PFS) in the BRCA-deficient Population (Arm 2 vs Arm 1) | 21.1 months |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Progression-Free Survival (PFS) in the BRCA-deficient Population (Arm 2 vs Arm 1) | 34.7 months |
Comparison: The secondary efficacy analyses compared investigator-assessed PFS in the Veliparib + Carboplatin + Paclitaxel -\> Placebo group (Arm 2) vs. the Placebo + Carboplatin + Paclitaxel -\> Placebo group (Arm 1).p-value: 0.33595% CI: [0.821, 1.799]Log Rank
Secondary
Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort (Arm 2 vs Arm 1)
PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death if disease progression was not reached. If the participant did not have an event of disease progression or death, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. The primary analysis of PFS occurred when the protocol-specified number of PFS events was reached and was performed in 3 sequentially inclusive populations. Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions. .
Time frame: From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.
Population: Analyses were performed in 3 sequentially inclusive populations. The second analysis was conducted using the HRD cohort which included participants in the BRCA-mutation cohort and those determined to have HRD tumors.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Carboplatin + Paclitaxel -> Placebo | Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort (Arm 2 vs Arm 1) | 20.5 months |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort (Arm 2 vs Arm 1) | 18.1 months |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort (Arm 2 vs Arm 1) | 31.9 months |
Comparison: The secondary efficacy analyses compared investigator-assessed PFS in the Veliparib + Carboplatin + Paclitaxel -\> Placebo group (Arm 2) vs. the Placebo + Carboplatin + Paclitaxel -\> Placebo group (Arm 1).p-value: 0.46295% CI: [0.855, 1.414]Log Rank
Secondary
Progression-Free Survival (PFS) in the Intention-to-treat Population (Arm 2 vs Arm 1)
PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death (all causes of mortality) if disease progression was not reached. If the participant did not have an event of disease progression according to RECIST criteria (as or death, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions. The primary analysis of PFS occurred when the protocol-specified number of PFS events was reached.
Time frame: From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.
Population: Analyses were performed in 3 sequentially inclusive populations. The third analysis was conducted using the intention-to-treat (ITT) population (all randomized participants).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Carboplatin + Paclitaxel -> Placebo | Progression-Free Survival (PFS) in the Intention-to-treat Population (Arm 2 vs Arm 1) | 17.3 months |
| Veliparib + Carboplatin + Paclitaxel -> Placebo | Progression-Free Survival (PFS) in the Intention-to-treat Population (Arm 2 vs Arm 1) | 15.2 months |
| Veliparib + Carboplatin + Paclitaxel -> Veliparib | Progression-Free Survival (PFS) in the Intention-to-treat Population (Arm 2 vs Arm 1) | 23.5 months |
Comparison: The secondary efficacy analyses compared investigator-assessed PFS in the Veliparib + Carboplatin + Paclitaxel -\> Placebo group (Arm 2) vs. the Placebo + Carboplatin + Paclitaxel -\> Placebo group (Arm 1).p-value: 0.4595% CI: [0.895, 1.287]Log Rank