Skip to content
Triangle logo TriangleGet started
← Full study record

NCT01120184 · OUTCOME

Time to Treatment Failure (TTF)

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 48 months from randomization until clinical cutoff of 16-Sept-2014

What was measured

Treatment failure was defined as the discontinuation of all study medications in the treatment arm for any reason including disease progression, treatment toxicity, death, physician decision, or participant withdrawal. TTF was defined as the time from randomization to treatment failure. Median TTF was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method.

Analysis population: ITT Population.

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 + Taxane365
Trastuzumab Emtansine + Placebo367
Trastuzumab Emtansine + Pertuzumab363

Reported measurements

Source class 1
Values in months · Interval/dispersion: 95% Confidence Interval
GroupValueSpreadLowerUpperComment
Trastuzumab + Taxane10.2Not reported9.211.8Not reported
Trastuzumab Emtansine + Placebo12.1Not reported9.913.9Not reported
Trastuzumab Emtansine + Pertuzumab11.8Not reported9.914.2Not reported

Source statistical analyses

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

  1. ci Lower Limit
    0.66
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    97.5
    ci Upper Limit
    0.97
    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
    0.80
  2. ci Lower Limit
    0.65
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    97.5
    ci Upper Limit
    0.95
    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
    0.78
Complete source fields
analyses
  1. ci Lower Limit
    0.66
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    97.5
    ci Upper Limit
    0.97
    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
    0.80
  2. ci Lower Limit
    0.65
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    97.5
    ci Upper Limit
    0.95
    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
    0.78
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        lower Limit
        9.2
        upper Limit
        11.8
        value
        10.2
      2. group Id
        OG001
        lower Limit
        9.9
        upper Limit
        13.9
        value
        12.1
      3. group Id
        OG002
        lower Limit
        9.9
        upper Limit
        14.2
        value
        11.8
denoms
  1. counts
    1. group Id
      OG000
      value
      365
    2. group Id
      OG001
      value
      367
    3. group Id
      OG002
      value
      363
    units
    Participants
description
Treatment failure was defined as the discontinuation of all study medications in the treatment arm for any reason including disease progression, treatment toxicity, death, physician decision, or participant withdrawal. TTF was defined as the time from randomization to treatment failure. Median TTF 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.
reporting Status
POSTED
time Frame
Up to 48 months from randomization until clinical cutoff of 16-Sept-2014
title
Time to Treatment Failure (TTF)
type
SECONDARY
unit Of Measure
months

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

Preserved source evidence · Not medical advice