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NCT01120184 · OUTCOME

Duration of Response According to IRF Assessment

A Study of Trastuzumab Emtansine (T-DM1) Plus Pertuzumab/Pertuzumab Placebo Versus Trastuzumab [Herceptin] Plus a Taxane in Participants With Metastatic Breast Cancer (MARIANNE) · Source last updated 2024-03-04

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
Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)

What was measured

Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. Duration of response was defined as the time from confirmed PR or CR to first documented disease progression or death from any cause. CR was defined as the disappearance of all target lesions and non-target lesions and short-axis reduction in pathological lymph nodes to \<10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. Median duration of response was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method.

Analysis population: ITT Population. Only participants achieving CR or PR were included in the analysis.

Groups in this outcome

Trastuzumab + Taxane

Participants received trastuzumab plus either docetaxel or paclitaxel. The regimen was chosen at the investigator's discretion. Option 1: trastuzumab 8 mg/kg via IV infusion on Day 1 of Cycle 1, then 6 mg/kg IV on Day 1 of each subsequent 3-week cycle; plus a minimum of 6 cycles with docetaxel 75 or 100 mg/m\^2 IV on Day 1 of each 3-week cycle. Option 2: trastuzumab 4 mg/kg IV on Day 1 of Cycle 1, then 2 mg/kg IV weekly beginning on Day 8 of Cycle 1; plus a minimum of 18 weeks with paclitaxel 80 mg/m\^2 IV weekly. Treatment continued until disease progression, unacceptable toxicity, or study termination. If trastuzumab or docetaxel were discontinued for toxicity, the other agent could be continued as monotherapy.

Trastuzumab Emtansine + Placebo

Participants received trastuzumab emtansine plus pertuzumab-placebo. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the placebo IV infusion, on Day 1 of each 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.

Trastuzumab Emtansine + Pertuzumab

Participants received trastuzumab emtansine plus pertuzumab. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the pertuzumab IV infusion, on Day 1 of each 3-week cycle. Pertuzumab was given as 840 mg IV on Day 1 of Cycle 1, then 420 mg IV on Day 1 of each subsequent 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.

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

Analysis denominator · Participants

GroupSource count
Trastuzumab + Taxane195
Trastuzumab Emtansine + Placebo181
Trastuzumab Emtansine + Pertuzumab192

Reported measurements

Source class 1
Values in months · Interval/dispersion: 95% Confidence Interval
GroupValueSpreadLowerUpperComment
Trastuzumab + Taxane12.5Not reported10.516.6Not reported
Trastuzumab Emtansine + Placebo20.7Not reported14.825.0Not reported
Trastuzumab Emtansine + Pertuzumab21.2Not reported15.829.3Not reported

Source statistical analyses

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

  1. ci Lower Limit
    0.43
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    97.5
    ci Upper Limit
    0.84
    estimate Comment
    Direction of comparison: Trastuzumab Emtansine + Placebo vs Trastuzumab + Taxane
    group Description
    Stratified Analysis: Stratification factors included world region (United States, Western Europe/Canada/Australia-Pacific, Eastern Europe, Asia, others); prior adjuvant/neoadjuvant therapy (no, yes \[trastuzumab and/or lapatinib\], yes \[no trastuzumab and/or lapatinib\]), and visceral disease (present, absent).
    group Ids
    1. OG000
    2. OG001
    non Inferiority Type
    SUPERIORITY_OR_OTHER_LEGACY
    param Type
    Hazard Ratio (HR)
    param Value
    0.60
  2. ci Lower Limit
    0.45
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    97.5
    ci Upper Limit
    0.85
    estimate Comment
    Direction of comparison: Trastuzumab Emtansine + Pertuzumab vs Trastuzumab + Taxane
    group Description
    Stratified Analysis: Stratification factors included world region (United States, Western Europe/Canada/Australia-Pacific, Eastern Europe, Asia, others); prior adjuvant/neoadjuvant therapy (no, yes \[trastuzumab and/or lapatinib\], yes \[no trastuzumab and/or lapatinib\]), and visceral disease (present, absent).
    group Ids
    1. OG000
    2. OG002
    non Inferiority Type
    SUPERIORITY_OR_OTHER_LEGACY
    param Type
    Hazard Ratio (HR)
    param Value
    0.62
Complete source fields
analyses
  1. ci Lower Limit
    0.43
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    97.5
    ci Upper Limit
    0.84
    estimate Comment
    Direction of comparison: Trastuzumab Emtansine + Placebo vs Trastuzumab + Taxane
    group Description
    Stratified Analysis: Stratification factors included world region (United States, Western Europe/Canada/Australia-Pacific, Eastern Europe, Asia, others); prior adjuvant/neoadjuvant therapy (no, yes \[trastuzumab and/or lapatinib\], yes \[no trastuzumab and/or lapatinib\]), and visceral disease (present, absent).
    group Ids
    1. OG000
    2. OG001
    non Inferiority Type
    SUPERIORITY_OR_OTHER_LEGACY
    param Type
    Hazard Ratio (HR)
    param Value
    0.60
  2. ci Lower Limit
    0.45
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    97.5
    ci Upper Limit
    0.85
    estimate Comment
    Direction of comparison: Trastuzumab Emtansine + Pertuzumab vs Trastuzumab + Taxane
    group Description
    Stratified Analysis: Stratification factors included world region (United States, Western Europe/Canada/Australia-Pacific, Eastern Europe, Asia, others); prior adjuvant/neoadjuvant therapy (no, yes \[trastuzumab and/or lapatinib\], yes \[no trastuzumab and/or lapatinib\]), and visceral disease (present, absent).
    group Ids
    1. OG000
    2. OG002
    non Inferiority Type
    SUPERIORITY_OR_OTHER_LEGACY
    param Type
    Hazard Ratio (HR)
    param Value
    0.62
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        lower Limit
        10.5
        upper Limit
        16.6
        value
        12.5
      2. group Id
        OG001
        lower Limit
        14.8
        upper Limit
        25.0
        value
        20.7
      3. group Id
        OG002
        lower Limit
        15.8
        upper Limit
        29.3
        value
        21.2
denoms
  1. counts
    1. group Id
      OG000
      value
      195
    2. group Id
      OG001
      value
      181
    3. group Id
      OG002
      value
      192
    units
    Participants
description
Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. Duration of response was defined as the time from confirmed PR or CR to first documented disease progression or death from any cause. CR was defined as the disappearance of all target lesions and non-target lesions and short-axis reduction in pathological lymph nodes to \<10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. Median duration of response was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method.
dispersion Type
95% Confidence Interval
groups
  1. description
    Participants received trastuzumab plus either docetaxel or paclitaxel. The regimen was chosen at the investigator's discretion. Option 1: trastuzumab 8 mg/kg via IV infusion on Day 1 of Cycle 1, then 6 mg/kg IV on Day 1 of each subsequent 3-week cycle; plus a minimum of 6 cycles with docetaxel 75 or 100 mg/m\^2 IV on Day 1 of each 3-week cycle. Option 2: trastuzumab 4 mg/kg IV on Day 1 of Cycle 1, then 2 mg/kg IV weekly beginning on Day 8 of Cycle 1; plus a minimum of 18 weeks with paclitaxel 80 mg/m\^2 IV weekly. Treatment continued until disease progression, unacceptable toxicity, or study termination. If trastuzumab or docetaxel were discontinued for toxicity, the other agent could be continued as monotherapy.
    id
    OG000
    title
    Trastuzumab + Taxane
  2. description
    Participants received trastuzumab emtansine plus pertuzumab-placebo. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the placebo IV infusion, on Day 1 of each 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.
    id
    OG001
    title
    Trastuzumab Emtansine + Placebo
  3. description
    Participants received trastuzumab emtansine plus pertuzumab. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the pertuzumab IV infusion, on Day 1 of each 3-week cycle. Pertuzumab was given as 840 mg IV on Day 1 of Cycle 1, then 420 mg IV on Day 1 of each subsequent 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.
    id
    OG002
    title
    Trastuzumab Emtansine + Pertuzumab
param Type
MEDIAN
population Description
ITT Population. Only participants achieving CR or PR were included in the analysis.
reporting Status
POSTED
time Frame
Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
title
Duration of Response According to IRF Assessment
type
SECONDARY
unit Of Measure
months

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Preserved source evidence · Not medical advice