An Open-label Study of Trastuzumab Emtansine (T-DM1) vs Capecitabine + Lapatinib in Patients With HER2-positive Locally Advanced or Metastatic Breast Cancer (EMILIA)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00829166
First received: January 22, 2009
Last updated: January 7, 2014
Last verified: January 2014
Results First Received: February 22, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Breast Cancer
Interventions: Drug: Trastuzumab emtansine [Kadcyla]
Drug: Lapatinib
Drug: Capecitabine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Trastuzumab Emtansine Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) over 30-90 minutes on Day 1 of each 21-day treatment cycle.
Lapatinib + Capecitabine Patients received lapatinib 1250 mg/day orally once per day of each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle.

Participant Flow:   Overall Study
    Trastuzumab Emtansine     Lapatinib + Capecitabine  
STARTED     495     496  
COMPLETED     308     262  
NOT COMPLETED     187     234  
Death                 149                 182  
Lost to Follow-up                 3                 1  
Physician's Decision                 4                 2  
Subject's Decision                 28                 48  
Reason Not Specified                 3                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Trastuzumab Emtansine Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) over 30-90 minutes on Day 1 of each 21-day treatment cycle.
Lapatinib + Capecitabine Patients received lapatinib 1250 mg/day orally once per day of each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle.
Total Total of all reporting groups

Baseline Measures
    Trastuzumab Emtansine     Lapatinib + Capecitabine     Total  
Number of Participants  
[units: participants]
  495     496     991  
Age  
[units: years]
Mean ± Standard Deviation
  52.2  ± 11.0     53.2  ± 10.8     52.7  ± 10.9  
Gender  
[units: participants]
     
Female     494     492     986  
Male     1     4     5  



  Outcome Measures
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1.  Primary:   Progression-free Survival (PFS) Assessed by an Independent Review Committee   [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]

Measure Type Primary
Measure Title Progression-free Survival (PFS) Assessed by an Independent Review Committee
Measure Description PFS was defined as the time from randomization to progressive disease (PD) or death from any cause, whichever occurred earlier. All measurable lesions up to a maximum of 5 per organ and 10 in total, representative of all involved organs, should be identified as target lesions (TL) and recorded and measured at baseline. TLs should be selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements either by imaging or clinically. A sum of the longest diameter for all TLs will be calculated and reported as the baseline sum longest diameter (SLD). All other lesions (or sites of disease) should be identified as non-TLs and recorded at baseline. PD for TLs was defined as ≥ 20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of 1 or more new lesions. PD for non-TLs was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs.
Time Frame From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population: All randomized patients on the basis of the treatment assigned at randomization.

Reporting Groups
  Description
Trastuzumab Emtansine Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) over 30-90 minutes on Day 1 of each 21-day treatment cycle.
Lapatinib + Capecitabine Patients received lapatinib 1250 mg/day orally once per day of each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle.

Measured Values
    Trastuzumab Emtansine     Lapatinib + Capecitabine  
Number of Participants Analyzed  
[units: participants]
  495     496  
Progression-free Survival (PFS) Assessed by an Independent Review Committee  
[units: Months]
Median ( 95% Confidence Interval )
  9.6  
  ( 8.25 to 10.64 )  
  6.4  
  ( 5.68 to 7.06 )  

No statistical analysis provided for Progression-free Survival (PFS) Assessed by an Independent Review Committee



2.  Primary:   Overall Survival   [ Time Frame: From the date of randomization through the data cut-off date of 31 Jul 2012 (up to 3 years, 5 months) ]

Measure Type Primary
Measure Title Overall Survival
Measure Description Overall survival was defined as the time from the date of randomization to the date of death from any cause. The results reported are from an interim analysis; results from the final analysis will be reported when the study is completed.
Time Frame From the date of randomization through the data cut-off date of 31 Jul 2012 (up to 3 years, 5 months)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population: All randomized patients on the basis of the treatment assigned at randomization.

Reporting Groups
  Description
Trastuzumab Emtansine Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) over 30-90 minutes on Day 1 of each 21-day treatment cycle.
Lapatinib + Capecitabine Patients received lapatinib 1250 mg/day orally once per day of each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle.

Measured Values
    Trastuzumab Emtansine     Lapatinib + Capecitabine  
Number of Participants Analyzed  
[units: participants]
  495     496  
Overall Survival  
[units: Months]
Median ( 95% Confidence Interval )
  30.9  
  ( 26.81 to 34.27 )  
  25.1  
  ( 22.74 to 27.96 )  

No statistical analysis provided for Overall Survival



3.  Primary:   1 and 2 Year Survival   [ Time Frame: From the date of randomization through the data cut-off date of 31 Jul 2012 (up to 3 years, 5 months) ]

Measure Type Primary
Measure Title 1 and 2 Year Survival
Measure Description 1 and 2 year survival were defined as the percentage of patients alive 1 and 2 years after starting treatment.
Time Frame From the date of randomization through the data cut-off date of 31 Jul 2012 (up to 3 years, 5 months)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population: All randomized patients on the basis of the treatment assigned at randomization.

Reporting Groups
  Description
Trastuzumab Emtansine Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) over 30-90 minutes on Day 1 of each 21-day treatment cycle.
Lapatinib + Capecitabine Patients received lapatinib 1250 mg/day orally once per day of each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle.

Measured Values
    Trastuzumab Emtansine     Lapatinib + Capecitabine  
Number of Participants Analyzed  
[units: participants]
  495     496  
1 and 2 Year Survival  
[units: Percentage of patients]
Number ( 95% Confidence Interval )
   
1-year Survival     85.2  
  ( 81.99 to 88.49 )  
  78.4  
  ( 74.62 to 82.26 )  
2-year Survival     64.7  
  ( 59.31 to 70.19 )  
  51.8  
  ( 45.92 to 57.73 )  

No statistical analysis provided for 1 and 2 Year Survival



4.  Secondary:   Progression-free Survival (PFS) Assessed by the Investigator   [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]

Measure Type Secondary
Measure Title Progression-free Survival (PFS) Assessed by the Investigator
Measure Description PFS was defined as the time from randomization to progressive disease (PD) or death from any cause, whichever occurred earlier. PD for TLs was defined as ≥ 20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of 1 or more new lesions. PD for non-TLs was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs.
Time Frame From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population: All randomized patients on the basis of the treatment assigned at randomization.

Reporting Groups
  Description
Trastuzumab Emtansine Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) over 30-90 minutes on Day 1 of each 21-day treatment cycle.
Lapatinib + Capecitabine Patients received lapatinib 1250 mg/day orally once per day of each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle.

Measured Values
    Trastuzumab Emtansine     Lapatinib + Capecitabine  
Number of Participants Analyzed  
[units: participants]
  495     496  
Progression-free Survival (PFS) Assessed by the Investigator  
[units: Months]
Median ( 95% Confidence Interval )
  9.4  
  ( 7.49 to 10.78 )  
  5.8  
  ( 5.59 to 6.93 )  

No statistical analysis provided for Progression-free Survival (PFS) Assessed by the Investigator



5.  Secondary:   Objective Response (OR) Assessed by the Independent Review Committee   [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]

Measure Type Secondary
Measure Title Objective Response (OR) Assessed by the Independent Review Committee
Measure Description OR was defined as the percentage of patients with a complete response (CR) or partial response (PR). For TLs, a CR was defined as the disappearance of all TLs and a PR was defined as ≥ 30% decrease in the SLD of TLs, taking as reference the baseline SLD. For non-TLs, a CR was defined as the disappearance of all non-TLs and a PR was defined as the persistence of 1 or more non-TLs.
Time Frame From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population: All randomized patients on the basis of the treatment assigned at randomization. Only patients with measurable disease at baseline were included in the analysis.

Reporting Groups
  Description
Trastuzumab Emtansine Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) over 30-90 minutes on Day 1 of each 21-day treatment cycle.
Lapatinib + Capecitabine Patients received lapatinib 1250 mg/day orally once per day of each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle.

Measured Values
    Trastuzumab Emtansine     Lapatinib + Capecitabine  
Number of Participants Analyzed  
[units: participants]
  397     389  
Objective Response (OR) Assessed by the Independent Review Committee  
[units: Percentage of patients]
Number ( 95% Confidence Interval )
  43.6  
  ( 38.6 to 48.6 )  
  30.8  
  ( 26.3 to 35.7 )  

No statistical analysis provided for Objective Response (OR) Assessed by the Independent Review Committee



6.  Secondary:   Duration of Objective Response (OR)   [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]

Measure Type Secondary
Measure Title Duration of Objective Response (OR)
Measure Description Duration of OR was defined as the time from first documented OR to first documented progressive disease (PD) or death from any cause, whichever occurred earlier. PD for target lesions was defined as ≥ 20% increase in the sum of the longest diameter, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of 1 or more new lesions. PD for non-target lesions was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.
Time Frame From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population: All randomized patients on the basis of the treatment assigned at randomization. Only patients with an objective response were included in the analysis.

Reporting Groups
  Description
Trastuzumab Emtansine Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) over 30-90 minutes on Day 1 of each 21-day treatment cycle.
Lapatinib + Capecitabine Patients received lapatinib 1250 mg/day orally once per day of each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle.

Measured Values
    Trastuzumab Emtansine     Lapatinib + Capecitabine  
Number of Participants Analyzed  
[units: participants]
  173     120  
Duration of Objective Response (OR)  
[units: Months]
Median ( 95% Confidence Interval )
  12.6  
  ( 8.38 to 20.76 )  
  6.5  
  ( 5.45 to 7.16 )  

No statistical analysis provided for Duration of Objective Response (OR)



7.  Secondary:   Clinical Benefit   [ Time Frame: 6 months after randomization ]

Measure Type Secondary
Measure Title Clinical Benefit
Measure Description Clinical benefit was defined as the percentage of patients with a complete response (CR), partial response (PR), or stable disease (SD) at 6 months after randomization. For target lesions a CR was defined as the disappearance of all target lesions, a PR was defined as ≥ 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. For non-target lesions, a CR was defined as the disappearance of all non-target lesions and a PR was defined as the persistence of 1 or more non-target lesions, and SD was defined as the persistence of 1 or more non-target lesion.
Time Frame 6 months after randomization  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population: All randomized patients on the basis of the treatment assigned at randomization. Only patients with measureable disease at Baseline were included in the analysis.

Reporting Groups
  Description
Trastuzumab Emtansine Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) over 30-90 minutes on Day 1 of each 21-day treatment cycle.
Lapatinib + Capecitabine Patients received lapatinib 1250 mg/day orally once per day of each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle.

Measured Values
    Trastuzumab Emtansine     Lapatinib + Capecitabine  
Number of Participants Analyzed  
[units: participants]
  397     389  
Clinical Benefit  
[units: Percentage of patients]
Number ( 95% Confidence Interval )
  58.2  
  ( 53.3 to 63.1 )  
  44.2  
  ( 39.2 to 49.2 )  

No statistical analysis provided for Clinical Benefit



8.  Secondary:   Time to Treatment Failure   [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]

Measure Type Secondary
Measure Title Time to Treatment Failure
Measure Description Time to treatment failure was defined as the time from randomization to discontinuation of treatment for any reason, including progressive disease (PD), treatment toxicity, or death from any cause. PD for target lesions was defined as ≥ 20% increase in the sum of the longest diameter, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of 1 or more new lesions. PD for non-target lesions was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.
Time Frame From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population: All randomized patients on the basis of the treatment assigned at randomization.

Reporting Groups
  Description
Trastuzumab Emtansine Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) over 30-90 minutes on Day 1 of each 21-day treatment cycle.
Lapatinib + Capecitabine Patients received lapatinib 1250 mg/day orally once per day of each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle.

Measured Values
    Trastuzumab Emtansine     Lapatinib + Capecitabine  
Number of Participants Analyzed  
[units: participants]
  495     496  
Time to Treatment Failure  
[units: Months]
Median ( 95% Confidence Interval )
  7.9  
  ( 6.41 to 9.00 )  
  5.8  
  ( 5.52 to 6.31 )  

No statistical analysis provided for Time to Treatment Failure



9.  Secondary:   Time to Symptom Progression   [ Time Frame: From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months) ]

Measure Type Secondary
Measure Title Time to Symptom Progression
Measure Description Time to symptom progression was defined as the time from randomization to the first symptom progression as measured by the Functional Assessment of Cancer Therapy-for patients with Breast Cancer (FACT-B) questionnaire with the Trial Outcomes Index-Physical/Functional/Breast (TOI-PFB) subscale. The FACT-B TOI-PFB subscale contains 24 items from 3 subsections of the FACT-B questionnaire: Physical well-being, functional well-being, and additional concerns for breast cancer patients (breast cancer subscale [BCS]). All items in the questionnaire were rated by the patient on a 5-point scale ranging from 0 ("not at all") to 4 ("very much"). The total score ranged from 0 to 96. A higher score indicates better perceived quality of life. A positive change score from baseline indicates improvement. Symptom progression was defined as a decrease from baseline of 5 points or more.
Time Frame From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population: All randomized patients on the basis of the treatment assigned at randomization. Only female patients with a baseline assessment and at least 1 follow-up assessment were included in the analysis.

Reporting Groups
  Description
Trastuzumab Emtansine Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) over 30-90 minutes on Day 1 of each 21-day treatment cycle.
Lapatinib + Capecitabine Patients received lapatinib 1250 mg/day orally once per day of each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle.

Measured Values
    Trastuzumab Emtansine     Lapatinib + Capecitabine  
Number of Participants Analyzed  
[units: participants]
  450     445  
Time to Symptom Progression  
[units: Months]
Median ( 95% Confidence Interval )
  7.1  
  ( 5.59 to 8.44 )  
  4.6  
  ( 4.14 to 5.78 )  

No statistical analysis provided for Time to Symptom Progression




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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