Skip to content
Triangle logo TriangleGet started
← Full study record

NCT01942135 · OUTCOME

Progression-Free Survival (PFS) as Assessed by the Investigator

Palbociclib (PD-0332991) Combined With Fulvestrant In Hormone Receptor+ HER2-Negative Metastatic Breast Cancer After Endocrine Failure (PALOMA-3) · Source last updated 2024-04-04

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 date to date of first documentation of progression or death (assessed up to 12 months)

What was measured

PFS is the time from the date of randomization to the date of the first documentation of objective progression of disease (PD)or death due to any cause in absence of documented PD. Participants lacking an evaluation of tumor response after randomization had their PFS time censored on the date of randomization with the duration of a day. Participants with documentation of PD or death after a long interval (2 or more incomplete or non-evaluable assessments) since the last tumor assessment were censored at the time of last objective assessment that did not show PD. The length of PFS was calculated as PFS time (months) =\[progression/death date(censor date) - randomization date + 1\]/30.4. Progression is defined using Response Evaluation Criteria in Solid Tumors(RECIST v1.1) a 20% increase in the sum of diameters of target lesions and the sum must also demonstrate an absolute increase of at least 5mm or unequivocal progression of existing non-target lesions or the appearance of new lesions.

Analysis population: The intent-to-treat (ITT) population or full analysis set included all participants who were randomized, with study intervention, regardless of whether participants received the study intervention or received a different drug from that to which they were randomized.

Groups in this outcome

Palbociclib + Fulvestrant

Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase. Maximum treatment duration was 105 cycles.

Placebo + Fulvestrant

Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase. Maximum treatment duration was 93 cycles.

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

Analysis denominator · Participants

GroupSource count
Palbociclib + Fulvestrant347
Placebo + Fulvestrant174

Reported measurements

Source class 1
Values in months · Interval/dispersion: 95% Confidence Interval
GroupValueSpreadLowerUpperComment
Palbociclib + Fulvestrant9.2Not reported7.5NANot estimable based on the Brookmeyer and Crowley method, because of insufficient number of participants with events.
Placebo + Fulvestrant3.8Not reported3.55.5Not reported

Source statistical analyses

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

  1. ci Lower Limit
    0.318
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    95
    ci Upper Limit
    0.560
    estimate Comment
    Assuming proportional hazards, a hazard ratio less than 1 indicates a reduction in hazard rate in favor of the palbociclib plus fulvestrant arm.
    group Description
    The primary hypothesis to be tested was H0: λ≥1 versus. HA: λ\<1, where λ was the palbociclib plus fulvestrant: placebo plus fulvestrant hazard ratio (HR). A HR less than 1 indicates a reduction in hazard rate in favor of Palbociclib + Fulvestrant. The study was planned to have 90% power and control the type-I error rate at 0.025.
    group Ids
    1. OG000
    2. OG001
    non Inferiority Type
    SUPERIORITY_OR_OTHER_LEGACY
    p Value
    <0.000001
    p Value Comment
    The overall Type-I error rate was persevered at 1-sided 0.025 level for the analysis of the primary endpoint PFS by the Haybittle-Peto efficacy boundary. The priori threshold for statistical significance was 0.00135.
    param Type
    Hazard Ratio (HR)
    param Value
    0.422
    statistical Comment
    The log rank test stratified by sensitivity to prior hormonal therapy and the presence of visceral metastases based on the randomization information.
    statistical Method
    Stratified Log Rank Test (1-sided)
Complete source fields
analyses
  1. ci Lower Limit
    0.318
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    95
    ci Upper Limit
    0.560
    estimate Comment
    Assuming proportional hazards, a hazard ratio less than 1 indicates a reduction in hazard rate in favor of the palbociclib plus fulvestrant arm.
    group Description
    The primary hypothesis to be tested was H0: λ≥1 versus. HA: λ\<1, where λ was the palbociclib plus fulvestrant: placebo plus fulvestrant hazard ratio (HR). A HR less than 1 indicates a reduction in hazard rate in favor of Palbociclib + Fulvestrant. The study was planned to have 90% power and control the type-I error rate at 0.025.
    group Ids
    1. OG000
    2. OG001
    non Inferiority Type
    SUPERIORITY_OR_OTHER_LEGACY
    p Value
    <0.000001
    p Value Comment
    The overall Type-I error rate was persevered at 1-sided 0.025 level for the analysis of the primary endpoint PFS by the Haybittle-Peto efficacy boundary. The priori threshold for statistical significance was 0.00135.
    param Type
    Hazard Ratio (HR)
    param Value
    0.422
    statistical Comment
    The log rank test stratified by sensitivity to prior hormonal therapy and the presence of visceral metastases based on the randomization information.
    statistical Method
    Stratified Log Rank Test (1-sided)
classes
  1. categories
    1. measurements
      1. comment
        Not estimable based on the Brookmeyer and Crowley method, because of insufficient number of participants with events.
        group Id
        OG000
        lower Limit
        7.5
        upper Limit
        NA
        value
        9.2
      2. group Id
        OG001
        lower Limit
        3.5
        upper Limit
        5.5
        value
        3.8
denoms
  1. counts
    1. group Id
      OG000
      value
      347
    2. group Id
      OG001
      value
      174
    units
    Participants
description
PFS is the time from the date of randomization to the date of the first documentation of objective progression of disease (PD)or death due to any cause in absence of documented PD. Participants lacking an evaluation of tumor response after randomization had their PFS time censored on the date of randomization with the duration of a day. Participants with documentation of PD or death after a long interval (2 or more incomplete or non-evaluable assessments) since the last tumor assessment were censored at the time of last objective assessment that did not show PD. The length of PFS was calculated as PFS time (months) =\[progression/death date(censor date) - randomization date + 1\]/30.4. Progression is defined using Response Evaluation Criteria in Solid Tumors(RECIST v1.1) a 20% increase in the sum of diameters of target lesions and the sum must also demonstrate an absolute increase of at least 5mm or unequivocal progression of existing non-target lesions or the appearance of new lesions.
dispersion Type
95% Confidence Interval
groups
  1. description
    Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase. Maximum treatment duration was 105 cycles.
    id
    OG000
    title
    Palbociclib + Fulvestrant
  2. description
    Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase. Maximum treatment duration was 93 cycles.
    id
    OG001
    title
    Placebo + Fulvestrant
param Type
MEDIAN
population Description
The intent-to-treat (ITT) population or full analysis set included all participants who were randomized, with study intervention, regardless of whether participants received the study intervention or received a different drug from that to which they were randomized.
reporting Status
POSTED
time Frame
From randomization date to date of first documentation of progression or death (assessed up to 12 months)
title
Progression-Free Survival (PFS) as Assessed by the Investigator
type
PRIMARY
unit Of Measure
months

Download exact source JSON → · Snapshot ctgov-results-191f4516d4760045304b24a0

Preserved source evidence · Not medical advice