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NCT02470585 · OUTCOME

Progression-Free Survival (PFS) in the BRCA-deficient Population (Arm 2 vs Arm 1)

Veliparib With Carboplatin and Paclitaxel and as Continuation Maintenance Therapy in Adults With Newly Diagnosed Stage III or IV, High-grade Serous, Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer · Source last updated 2024-10-26

Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.

Measure
MEDIAN
Unit
months
Interval / dispersion
95% Confidence Interval
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.

What was measured

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.

Analysis 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.

Groups in this outcome

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.

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.

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.

Group identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.

Analysis denominator · Participants

GroupSource count
Placebo + Carboplatin + Paclitaxel -> Placebo92
Veliparib + Carboplatin + Paclitaxel -> Placebo98
Veliparib + Carboplatin + Paclitaxel -> Veliparib108

Reported measurements

Source class 1
Values in months · Interval/dispersion: 95% Confidence Interval
GroupValueSpreadLowerUpperComment
Placebo + Carboplatin + Paclitaxel -> Placebo22.0Not reported17.829.1Not reported
Veliparib + Carboplatin + Paclitaxel -> Placebo21.1Not reported17.025.5Not reported
Veliparib + Carboplatin + Paclitaxel -> Veliparib34.7Not reported31.8NACould not be estimated due to the low number of events

Source statistical analyses

Group order, estimate direction, methods and comments are retained. No treatment ranking is inferred.

  1. ci Lower Limit
    0.821
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    95
    ci Upper Limit
    1.799
    estimate Comment
    Cox proportional hazards model stratified according to the same factors as those used in the log-rank test above.
    group Description
    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).
    group Ids
    1. OG000
    2. OG001
    non Inferiority Comment
    Multiplicity considerations included 3 treatment arms, (2 pairwise comparisons), 3 sequentially inclusive populations (BRCA-mutation population, HRD population, and ITT population), and multiple endpoints. A fixed-sequence testing procedure was used to control the Type I error rate at 0.05 from the primary efficacy endpoints sequentially through the secondary efficacy endpoints.
    non Inferiority Type
    SUPERIORITY
    p Value
    0.335
    param Type
    Hazard Ratio (HR)
    param Value
    1.215
    statistical Comment
    Stratified according to residual disease status and disease stage.
    statistical Method
    Log Rank
Complete source fields
analyses
  1. ci Lower Limit
    0.821
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    95
    ci Upper Limit
    1.799
    estimate Comment
    Cox proportional hazards model stratified according to the same factors as those used in the log-rank test above.
    group Description
    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).
    group Ids
    1. OG000
    2. OG001
    non Inferiority Comment
    Multiplicity considerations included 3 treatment arms, (2 pairwise comparisons), 3 sequentially inclusive populations (BRCA-mutation population, HRD population, and ITT population), and multiple endpoints. A fixed-sequence testing procedure was used to control the Type I error rate at 0.05 from the primary efficacy endpoints sequentially through the secondary efficacy endpoints.
    non Inferiority Type
    SUPERIORITY
    p Value
    0.335
    param Type
    Hazard Ratio (HR)
    param Value
    1.215
    statistical Comment
    Stratified according to residual disease status and disease stage.
    statistical Method
    Log Rank
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        lower Limit
        17.8
        upper Limit
        29.1
        value
        22.0
      2. group Id
        OG001
        lower Limit
        17.0
        upper Limit
        25.5
        value
        21.1
      3. comment
        Could not be estimated due to the low number of events
        group Id
        OG002
        lower Limit
        31.8
        upper Limit
        NA
        value
        34.7
denoms
  1. counts
    1. group Id
      OG000
      value
      92
    2. group Id
      OG001
      value
      98
    3. group Id
      OG002
      value
      108
    units
    Participants
description
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.
dispersion Type
95% Confidence Interval
groups
  1. description
    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.
    id
    OG000
    title
    Placebo + Carboplatin + Paclitaxel -> Placebo
  2. description
    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.
    id
    OG001
    title
    Veliparib + Carboplatin + Paclitaxel -> Placebo
  3. description
    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.
    id
    OG002
    title
    Veliparib + Carboplatin + Paclitaxel -> Veliparib
param Type
MEDIAN
population Description
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.
reporting Status
POSTED
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.
title
Progression-Free Survival (PFS) in the BRCA-deficient Population (Arm 2 vs Arm 1)
type
SECONDARY
unit Of Measure
months

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Preserved source evidence · Not medical advice