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NCT02470585 · OUTCOME

Progression-Free Survival (PFS) in the Intention-to-treat Population (Arm 3 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 (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.

Analysis population: Analyses were performed in 3 sequentially inclusive populations. The third analysis was conducted using the intention-to-treat (ITT) population (all randomized participants).

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 -> Placebo375
Veliparib + Carboplatin + Paclitaxel -> Placebo383
Veliparib + Carboplatin + Paclitaxel -> Veliparib382

Reported measurements

Source class 1
Values in months · Interval/dispersion: 95% Confidence Interval
GroupValueSpreadLowerUpperComment
Placebo + Carboplatin + Paclitaxel -> Placebo17.3Not reported15.119.1Not reported
Veliparib + Carboplatin + Paclitaxel -> Placebo15.2Not reported14.117.3Not reported
Veliparib + Carboplatin + Paclitaxel -> Veliparib23.5Not reported19.326.3Not reported

Source statistical analyses

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

  1. ci Lower Limit
    0.562
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    95
    ci Upper Limit
    0.831
    estimate Comment
    Cox proportional hazards model stratified according to the same factors as those used in the log-rank test above.
    group Description
    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).
    group Ids
    1. OG000
    2. OG002
    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
    <0.001
    p Value Comment
    A 2-sided p-value of ≤ 0.05 was considered statistically significant in the following hierarchical testing sequence: PFS was to be compared first in the BRCA-mutation cohort, then in the HRD cohort, and then in the ITT population.
    param Type
    Hazard Ratio (HR)
    param Value
    0.683
    statistical Comment
    Stratified according to residual disease status and disease stage, choice of the paclitaxel regimen, and BRCA-mutation status
    statistical Method
    Log Rank
Complete source fields
analyses
  1. ci Lower Limit
    0.562
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    95
    ci Upper Limit
    0.831
    estimate Comment
    Cox proportional hazards model stratified according to the same factors as those used in the log-rank test above.
    group Description
    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).
    group Ids
    1. OG000
    2. OG002
    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
    <0.001
    p Value Comment
    A 2-sided p-value of ≤ 0.05 was considered statistically significant in the following hierarchical testing sequence: PFS was to be compared first in the BRCA-mutation cohort, then in the HRD cohort, and then in the ITT population.
    param Type
    Hazard Ratio (HR)
    param Value
    0.683
    statistical Comment
    Stratified according to residual disease status and disease stage, choice of the paclitaxel regimen, and BRCA-mutation status
    statistical Method
    Log Rank
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        lower Limit
        15.1
        upper Limit
        19.1
        value
        17.3
      2. group Id
        OG001
        lower Limit
        14.1
        upper Limit
        17.3
        value
        15.2
      3. group Id
        OG002
        lower Limit
        19.3
        upper Limit
        26.3
        value
        23.5
denoms
  1. counts
    1. group Id
      OG000
      value
      375
    2. group Id
      OG001
      value
      383
    3. group Id
      OG002
      value
      382
    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 (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.
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 third analysis was conducted using the intention-to-treat (ITT) population (all randomized participants).
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 Intention-to-treat Population (Arm 3 vs Arm 1)
type
PRIMARY
unit Of Measure
months

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Preserved source evidence · Not medical advice