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NCT01704287 · OUTCOME

Progression-free Survival (PFS) - Initial Treatment Period

Study of Pembrolizumab (MK-3475) Versus Chemotherapy in Participants With Advanced Melanoma (MK-3475-002/P08719/KEYNOTE-002) · Source last updated 2020-05-18

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
Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015)

What was measured

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1), PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. Analysis of PFS was based on an integrated radiology and oncology (IRO) assessment and was not planned or conducted for the switch-to-pembrolizumab treatment groups. Median PFS based on the product limit (Kaplan-Meier) method for censored data is presented. This was the final analysis for PFS.

Analysis population: The analysis population consisted of all randomized participants. Participants were included in the initial treatment group to which they were randomized for the efficacy analysis.

Groups in this outcome

Pembrolizumab 2 mg/kg

Participants were initially randomized to receive pembrolizumab 2 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to \~66 months)

Pembrolizumab 10 mg/kg

Participants were initially randomized to receive pembrolizumab 10 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to \~66 months)

Investigator-Choice Chemotherapy (ICC)

Participants were initially randomized to receive 1 of 4 possible chemotherapy regimens decided at the treating institution (carboplatin+paclitaxel, paclitaxel alone, dacarbazine, or temozolomide). Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to \~66 months)

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

Analysis denominator · Participants

GroupSource count
Pembrolizumab 2 mg/kg180
Pembrolizumab 10 mg/kg181
Investigator-Choice Chemotherapy (ICC)179

Reported measurements

Source class 1
Values in Months · Interval/dispersion: 95% Confidence Interval
GroupValueSpreadLowerUpperComment
Pembrolizumab 2 mg/kg2.9Not reported2.83.8Not reported
Pembrolizumab 10 mg/kg3.0Not reported2.85.2Not reported
Investigator-Choice Chemotherapy (ICC)2.8Not reported2.62.8Not reported

Source statistical analyses

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

  1. ci Lower Limit
    0.46
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    95
    ci Upper Limit
    0.73
    estimate Comment
    Numerator=Pembrolizumab 2 mg/kg Denominator=ICC
    group Ids
    1. OG000
    2. OG002
    non Inferiority Comment
    Cox regression model with treatment as covariate stratified by Eastern Cooperative Oncology Group (ECOG) performance status (0 vs. 1); lactate dehydrogenase (LDH) levels (normal vs. elevated LDH levels \[≥110% Upper Limit of Normal (ULN)\]); \& BRAF mutational status (mutant vs. wild-type)
    non Inferiority Type
    SUPERIORITY_OR_OTHER_LEGACY
    p Value
    <0.0001
    p Value Comment
    One-sided p-value based on stratified log rank test
    param Type
    Hazard Ratio (HR)
    param Value
    0.58
    statistical Method
    Log Rank
  2. ci Lower Limit
    0.37
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    95
    ci Upper Limit
    0.60
    estimate Comment
    Numerator=Pembrolizumab 10 mg/kg Denominator=ICC
    group Ids
    1. OG001
    2. OG002
    non Inferiority Comment
    Cox regression model with treatment as covariate stratified by ECOG performance status (0 vs. 1); LDH levels (normal vs. elevated LDH levels \[≥110% ULN\]); \& BRAF mutational status (mutant vs. wild-type)
    non Inferiority Type
    SUPERIORITY_OR_OTHER_LEGACY
    p Value
    <0.0001
    p Value Comment
    One-sided p-value based on stratified log rank test
    param Type
    Hazard Ratio (HR)
    param Value
    0.47
    statistical Method
    Log Rank
  3. ci Lower Limit
    0.66
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    95
    ci Upper Limit
    1.05
    estimate Comment
    Numerator=Pembrolizumab 10 mg/kg Denominator=Pembrolizumab 2 mg/kg
    group Ids
    1. OG000
    2. OG001
    non Inferiority Comment
    Cox regression model with treatment as covariate stratified by ECOG performance status (0 vs. 1); LDH levels (normal vs. elevated LDH levels \[≥110% ULN\]); \& BRAF mutational status (mutant vs. wild-type)
    non Inferiority Type
    SUPERIORITY_OR_OTHER_LEGACY
    p Value
    0.1247
    p Value Comment
    Two-sided p-value based on stratified log rank test
    param Type
    Hazard Ratio (HR)
    param Value
    0.83
    statistical Method
    Log Rank
Complete source fields
analyses
  1. ci Lower Limit
    0.46
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    95
    ci Upper Limit
    0.73
    estimate Comment
    Numerator=Pembrolizumab 2 mg/kg Denominator=ICC
    group Ids
    1. OG000
    2. OG002
    non Inferiority Comment
    Cox regression model with treatment as covariate stratified by Eastern Cooperative Oncology Group (ECOG) performance status (0 vs. 1); lactate dehydrogenase (LDH) levels (normal vs. elevated LDH levels \[≥110% Upper Limit of Normal (ULN)\]); \& BRAF mutational status (mutant vs. wild-type)
    non Inferiority Type
    SUPERIORITY_OR_OTHER_LEGACY
    p Value
    <0.0001
    p Value Comment
    One-sided p-value based on stratified log rank test
    param Type
    Hazard Ratio (HR)
    param Value
    0.58
    statistical Method
    Log Rank
  2. ci Lower Limit
    0.37
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    95
    ci Upper Limit
    0.60
    estimate Comment
    Numerator=Pembrolizumab 10 mg/kg Denominator=ICC
    group Ids
    1. OG001
    2. OG002
    non Inferiority Comment
    Cox regression model with treatment as covariate stratified by ECOG performance status (0 vs. 1); LDH levels (normal vs. elevated LDH levels \[≥110% ULN\]); \& BRAF mutational status (mutant vs. wild-type)
    non Inferiority Type
    SUPERIORITY_OR_OTHER_LEGACY
    p Value
    <0.0001
    p Value Comment
    One-sided p-value based on stratified log rank test
    param Type
    Hazard Ratio (HR)
    param Value
    0.47
    statistical Method
    Log Rank
  3. ci Lower Limit
    0.66
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    95
    ci Upper Limit
    1.05
    estimate Comment
    Numerator=Pembrolizumab 10 mg/kg Denominator=Pembrolizumab 2 mg/kg
    group Ids
    1. OG000
    2. OG001
    non Inferiority Comment
    Cox regression model with treatment as covariate stratified by ECOG performance status (0 vs. 1); LDH levels (normal vs. elevated LDH levels \[≥110% ULN\]); \& BRAF mutational status (mutant vs. wild-type)
    non Inferiority Type
    SUPERIORITY_OR_OTHER_LEGACY
    p Value
    0.1247
    p Value Comment
    Two-sided p-value based on stratified log rank test
    param Type
    Hazard Ratio (HR)
    param Value
    0.83
    statistical Method
    Log Rank
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        lower Limit
        2.8
        upper Limit
        3.8
        value
        2.9
      2. group Id
        OG001
        lower Limit
        2.8
        upper Limit
        5.2
        value
        3.0
      3. group Id
        OG002
        lower Limit
        2.6
        upper Limit
        2.8
        value
        2.8
denoms
  1. counts
    1. group Id
      OG000
      value
      180
    2. group Id
      OG001
      value
      181
    3. group Id
      OG002
      value
      179
    units
    Participants
description
PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1), PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. Analysis of PFS was based on an integrated radiology and oncology (IRO) assessment and was not planned or conducted for the switch-to-pembrolizumab treatment groups. Median PFS based on the product limit (Kaplan-Meier) method for censored data is presented. This was the final analysis for PFS.
dispersion Type
95% Confidence Interval
groups
  1. description
    Participants were initially randomized to receive pembrolizumab 2 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to \~66 months)
    id
    OG000
    title
    Pembrolizumab 2 mg/kg
  2. description
    Participants were initially randomized to receive pembrolizumab 10 mg/kg IV Q3W. With Amendment 03, this dosing was discontinued and all study participants were to be treated with fixed-dose open label pembrolizumab 200 mg IV Q3W. Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to \~66 months)
    id
    OG001
    title
    Pembrolizumab 10 mg/kg
  3. description
    Participants were initially randomized to receive 1 of 4 possible chemotherapy regimens decided at the treating institution (carboplatin+paclitaxel, paclitaxel alone, dacarbazine, or temozolomide). Participants were to receive study drug until discontinuation due to progression of disease, toxicity, or choice. (Up to \~66 months)
    id
    OG002
    title
    Investigator-Choice Chemotherapy (ICC)
param Type
MEDIAN
population Description
The analysis population consisted of all randomized participants. Participants were included in the initial treatment group to which they were randomized for the efficacy analysis.
reporting Status
POSTED
time Frame
Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015)
title
Progression-free Survival (PFS) - Initial Treatment Period
type
PRIMARY
unit Of Measure
Months

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Preserved source evidence · Not medical advice