The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Trastuzumab Emtansine Versus Capecitabine + Lapatinib in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer (EMILIA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00829166
Recruitment Status : Completed
First Posted : January 26, 2009
Results First Posted : April 23, 2013
Last Update Posted : October 31, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Drug: Trastuzumab emtansine
Drug: Lapatinib
Drug: Capecitabine
Enrollment 991
Recruitment Details  
Pre-assignment Details Participants of "Lapatinib + Capecitabine" arm were allowed to cross over to receive trastuzumab emtansine based on statistically significant Overall Survival (OS) benefit in favor of trastuzumab emtansine demonstrated in second interim analysis (cut-off date 31 July 2012). The safety analysis of the arm was then reported.
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine
Hide Arm/Group Description Participants received trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) intravenous (IV) infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until disease progression (PD) (as assessed by the investigator), unmanageable toxicity, or study termination. Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 milligrams per square meter (mg/m^2) orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
Period Title: Overall Study
Started 495 496
Treated 490 488
Completed 0 0
Not Completed 495 496
Reason Not Completed
Death             305             333
Lost to Follow-up             5             4
Physician's Decision             4             3
Subject's Decision             41             55
Sponsor's Decision             137             98
Reason Not Specified             3             3
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine Total
Hide Arm/Group Description Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis. Total of all reporting groups
Overall Number of Baseline Participants 495 496 991
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included all randomized participants on the basis of the treatment assigned at randomization.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 495 participants 496 participants 991 participants
52.2  (11.0) 53.2  (10.8) 52.7  (10.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 495 participants 496 participants 991 participants
Female
494
  99.8%
492
  99.2%
986
  99.5%
Male
1
   0.2%
4
   0.8%
5
   0.5%
1.Primary Outcome
Title Percentage of Participants With PD or Death as Assessed by an Independent Review Committee (IRC)
Hide Description PD was assessed by an IRC using modified Response Evaluation Criteria in Solid Tumors (RECIST). All measurable lesions up to a maximum of 5 per organ and 10 in total were identified as target lesions (TLs) and recorded 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 was calculated as 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 greater than or equal to (>/=) 20 percent (%) increase in SLD, taking as reference smallest SLD recorded since treatment started or appearance of 1 or more new lesions. PD for non-TLs was defined as appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. Percentage of Participants with PD by IRC or death from any cause was reported.
Time Frame From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants on the basis of the treatment assigned at randomization.
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine
Hide Arm/Group Description:
Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
Overall Number of Participants Analyzed 495 496
Measure Type: Number
Unit of Measure: percentage of participants
53.5 61.3
2.Primary Outcome
Title Progression-free Survival (PFS) as Assessed by an IRC (Co-primary Endpoint)
Hide Description Tumor response was assessed by an IRC according to modified RECIST. All measurable lesions up to a maximum of 5 per organ and 10 in total were identified as TLs (on the basis of their size and their suitability for accurate repeated measurements either by imaging or clinically) and recorded at baseline. A sum of the longest diameter for all TLs was calculated as baseline SLD. All other lesions were identified as non-TLs and recorded at baseline. PD for TLs: >/= 20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or appearance of 1 or more new lesions. PD for non-TLs: appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. PFS: time from randomization to first documented PD by IRC or death from any cause (whichever occurred earlier). The median duration of PFS was estimated using Kaplan-Meier method. The 95% confidence interval (CI) was computed using the method of Brookmeyer and Crowley.
Time Frame From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants on the basis of the treatment assigned at randomization.
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine
Hide Arm/Group Description:
Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
Overall Number of Participants Analyzed 495 496
Median (95% Confidence Interval)
Unit of Measure: Months
9.6
(8.25 to 10.64)
6.4
(5.68 to 7.06)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine, Lapatinib + Capecitabine
Comments Analysis stratified by region of enrollment, number of prior chemotherapeutic regimens (0-1 or greater than [>] 1), and visceral/ non-visceral disease.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.650
Confidence Interval (2-Sided) 95%
0.549 to 0.771
Estimation Comments HR (relative to Lapatinib + Capecitabine) was estimated by Cox regression.
3.Primary Outcome
Title Percentage of Participants Who Died: Second Interim Analysis
Hide Description The percentage of participants who died from any cause was reported. The results are reported from second interim analysis, which deemed to be the confirmatory.
Time Frame From the date of randomization through the data cut-off date of 31 Jul 2012 (up to 3 years, 5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants on the basis of the treatment assigned at randomization.
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine
Hide Arm/Group Description:
Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
Overall Number of Participants Analyzed 495 496
Measure Type: Number
Unit of Measure: percentage of participants
30.1 36.7
4.Primary Outcome
Title Overall Survival: Second Interim Analysis (Co-primary Endpoint)
Hide Description OS was defined as the time from the date of randomization to the date of death from any cause. The median duration of OS was estimated using Kaplan-Meier method. The 95% CI was computed using the method of Brookmeyer and Crowley. The results are reported from second interim analysis, which deemed to be the confirmatory.
Time Frame From the date of randomization through the data cut-off date of 31 Jul 2012 (up to 3 years, 5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants on the basis of the treatment assigned at randomization.
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine
Hide Arm/Group Description:
Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
Overall Number of Participants Analyzed 495 496
Median (95% Confidence Interval)
Unit of Measure: Months
30.9
(26.81 to 34.27)
25.1
(22.74 to 27.96)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine, Lapatinib + Capecitabine
Comments Analysis stratified by region of enrollment, number of prior chemotherapeutic regimens (0-1 or >1), and visceral/ non-visceral disease.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.682
Confidence Interval (2-Sided) 95%
0.548 to 0.849
Estimation Comments HR (relative to Lapatinib + Capecitabine) was estimated by Cox regression.
5.Primary Outcome
Title Percentage of Participants Who Died: Final Analysis
Hide Description The percentage of participants who died from any cause was reported. The results reported are from the final analysis. The final analysis is descriptive.
Time Frame From the date of randomization through the data cut-off date of 31 Dec 2014 (up to 5 years, 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants on the basis of the treatment assigned at randomization.
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine
Hide Arm/Group Description:
Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
Overall Number of Participants Analyzed 495 496
Measure Type: Number
Unit of Measure: percentage of participants
61.2 67.1
6.Primary Outcome
Title Overall Survival: Final Analysis
Hide Description OS was defined as the time from the date of randomization to the date of death from any cause. The median duration of OS was estimated using Kaplan-Meier method. The 95% CI was computed using the method of Brookmeyer and Crowley. The results reported are from the final analysis. The final analysis is descriptive.
Time Frame From the date of randomization through the data cut-off date of 31 Dec 2014 (up to 5 years, 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants on the basis of the treatment assigned at randomization.
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine
Hide Arm/Group Description:
Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
Overall Number of Participants Analyzed 495 496
Median (95% Confidence Interval)
Unit of Measure: Months
29.9
(26.32 to 34.10)
25.9
(22.74 to 28.32)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine, Lapatinib + Capecitabine
Comments Analysis stratified by region of enrollment, number of prior chemotherapeutic regimens (0-1 or >1), and visceral/ non-visceral disease.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.749
Confidence Interval (2-Sided) 95%
0.639 to 0.877
Estimation Comments HR (relative to Lapatinib + Capecitabine) was estimated by Cox regression.
7.Primary Outcome
Title Percentage of Participants Who Were Alive at Year 1
Hide Description 1 year survival was defined as the percentage of participants alive 1 year after starting treatment. The results reported are from the final analysis.
Time Frame Year 1
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants on the basis of the treatment assigned at randomization.
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine
Hide Arm/Group Description:
Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
Overall Number of Participants Analyzed 495 496
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
85.3
(82.15 to 88.54)
78.9
(75.19 to 82.65)
8.Primary Outcome
Title Percentage of Participants Who Were Alive at Year 2
Hide Description 2 year survival was defined as the percentage of participants alive 2 years after starting treatment. The results reported are from the final analysis.
Time Frame Year 2
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants on the basis of the treatment assigned at randomization.
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine
Hide Arm/Group Description:
Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
Overall Number of Participants Analyzed 495 496
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
59.6
(55.10 to 64.06)
52.4
(47.81 to 57.08)
9.Secondary Outcome
Title Percentage of Participants With PD or Death as Assessed by the Investigator
Hide Description PD was assessed by the investigator using modified RECIST. All measurable lesions up to a maximum of 5 per organ and 10 in total were identified as TLs and recorded at baseline. A sum of the longest diameter for all TLs was calculated as baseline SLD. 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 appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. The percentage of participants who died or experienced PD by Investigator was reported.
Time Frame From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants on the basis of the treatment assigned at randomization.
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine
Hide Arm/Group Description:
Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
Overall Number of Participants Analyzed 495 496
Measure Type: Number
Unit of Measure: percentage of participants
58.0 67.5
10.Secondary Outcome
Title PFS as Assessed by the Investigator
Hide Description Tumor response was assessed by the investigator according to modified RECIST. All measurable lesions up to a maximum of 5 per organ and 10 in total were identified as TLs and recorded at baseline. A sum of the longest diameter for all TLs was calculated as baseline SLD. 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 appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. PFS was defined as the time from randomization to first documented PD by Investigator or death from any cause (whichever occurred earlier). The median duration of PFS was estimated using Kaplan-Meier method. The 95% CI was computed using the method of Brookmeyer and Crowley.
Time Frame From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants on the basis of the treatment assigned at randomization.
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine
Hide Arm/Group Description:
Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
Overall Number of Participants Analyzed 495 496
Median (95% Confidence Interval)
Unit of Measure: Months
9.4
(7.49 to 10.78)
5.8
(5.59 to 6.93)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine, Lapatinib + Capecitabine
Comments Analysis stratified by region of enrollment, number of prior chemotherapeutic regimens (0-1 or >1), and visceral/ non-visceral disease.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.658
Confidence Interval (2-Sided) 95%
0.560 to 0.774
Estimation Comments HR (relative to Lapatinib + Capecitabine) was estimated by Cox regression.
11.Secondary Outcome
Title Percentage of Participants With Objective Response (OR) as Assessed by an IRC
Hide Description Tumor response was assessed by an IRC according to modified RECIST. OR was defined as the percentage of participants with a complete response (CR) or partial response (PR). All measurable lesions up to a maximum of 5 per organ and 10 in total were identified as TLs and recorded at baseline. A sum of the longest diameter for all TLs was calculated as baseline SLD. 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. Confirmation of response at a consecutive tumor assessment at least 4 weeks apart was required. Participants without a post-baseline tumor assessment were considered non-responders. The percentage of participants with CR or PR by IRC was reported. The 95% CI was computed using Blyth-Still Casella exact CI method.
Time Frame From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants on the basis of the treatment assigned at randomization. Only participants with measurable disease at baseline were included in the analysis.
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine
Hide Arm/Group Description:
Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
Overall Number of Participants Analyzed 397 389
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
43.6
(38.6 to 48.6)
30.8
(26.3 to 35.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine, Lapatinib + Capecitabine
Comments Analysis stratified by region of enrollment, number of prior chemotherapeutic regimens (0-1 or >1), and visceral/ non-visceral disease.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Mantel-Haenszel chi-squared test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Objective Response Rates
Estimated Value 12.7
Confidence Interval (2-Sided) 95%
6.0 to 19.4
Estimation Comments The 95% CI for the difference in objective response rate (Trastuzumab emtansine minus Lapatinib + Capecitabine) was computed by using the approximate normal method.
12.Secondary Outcome
Title Duration of Objective Response (DOR) as Assessed by an IRC
Hide Description Tumor response was assessed by an IRC according to modified RECIST. DOR was defined as the time from first documented OR to first documented PD or death from any cause, whichever occurred earlier. OR was defined as a CR or PR determined on 2 consecutive tumor assessments at least 4 weeks apart. For TLs, CR was defined as the disappearance of all TLs; PR was defined as >/=30% decrease in the SLD of TLs, taking as reference the baseline SLD; and PD 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. For non-TLs, CR was defined as the disappearance of all non-TLs; PR was defined as the persistence of 1 or more non-TLs; and PD was defined as appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. The 95% CI was computed using the method of Brookmeyer and Crowley.
Time Frame From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants on the basis of the treatment assigned at randomization. Only participants with an objective response were included in the analysis.
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine
Hide Arm/Group Description:
Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
Overall Number of Participants Analyzed 173 120
Median (95% Confidence Interval)
Unit of Measure: Months
12.6
(8.38 to 20.76)
6.5
(5.45 to 7.16)
13.Secondary Outcome
Title Percentage of Participants With Clinical Benefit as Assessed by an IRC
Hide Description Tumor response was assessed by an IRC according to modified RECIST. Participants were considered as experienced clinical benefit if they had an OR or maintained stable disease (SD) for at least 6 months from randomization. OR: CR or PR determined on 2 consecutive tumor assessments >/=4 weeks apart. For TLs, CR: disappearance of all TLs; PR: >/=30% decrease in the SLD of TLs, taking as reference the baseline SLD; PD: >/=20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or appearance of 1 or more new lesions; and SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. For non-TLs, CR: disappearance of all non-TLs; PR/SD: persistence of 1 or more non-TLs; and PD: appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. Participants without a post-baseline tumor assessment were considered non-responders. The 95% CI was computed using Blyth-Still Casella exact CI method.
Time Frame From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants on the basis of the treatment assigned at randomization. Only participants with measurable disease at Baseline were included in the analysis.
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine
Hide Arm/Group Description:
Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
Overall Number of Participants Analyzed 397 389
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
58.2
(53.3 to 63.1)
44.2
(39.2 to 49.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine, Lapatinib + Capecitabine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Clinical Benefit Rate
Estimated Value 14
Confidence Interval (2-Sided) 95%
7.0 to 20.9
Estimation Comments The 95% CI for the difference in clinical benefit rate (Trastuzumab emtansine minus Lapatinib + Capecitabine) was computed by using the normal approximation method.
14.Secondary Outcome
Title Percentage of Participants With Treatment Failure
Hide Description Treatment failure was defined as discontinuation of treatment for any reason, including PD (per investigator review), treatment toxicity, or death from any cause. For "Lapatinib + Capecitabine" arm, a participant was considered as treatment failure only if both drugs were discontinued. For TLs, PD 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. For non-TLs, PD was defined as appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. Percentage of participants with treatment failure was reported.
Time Frame From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants on the basis of the treatment assigned at randomization.
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine
Hide Arm/Group Description:
Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
Overall Number of Participants Analyzed 495 496
Measure Type: Number
Unit of Measure: percentage of participants
63.2 74.8
15.Secondary Outcome
Title Time to Treatment Failure
Hide Description Time to treatment failure was defined as the time from randomization to discontinuation of treatment for any reason, including PD (per investigator review), treatment toxicity, or death from any cause. For "Lapatinib + Capecitabine" arm, a participant was considered as treatment failure only if both drugs were discontinued with treatment failure date as the later of the 2 discontinuation dates. For TLs, PD 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. For non-TLs, PD was defined as appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. The median time to treatment failure was estimated using Kaplan-Meier method. The 95% CI was computed using the method of Brookmeyer and Crowley.
Time Frame From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants on the basis of the treatment assigned at randomization.
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine
Hide Arm/Group Description:
Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
Overall Number of Participants Analyzed 495 496
Median (95% Confidence Interval)
Unit of Measure: Months
7.9
(6.41 to 9.00)
5.8
(5.52 to 6.31)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine, Lapatinib + Capecitabine
Comments Analysis stratified by region of enrollment, number of prior chemotherapeutic regimens (0-1 or >1), and visceral/ non-visceral disease.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.703
Confidence Interval (2-Sided) 95%
0.602 to 0.820
Estimation Comments HR (relative to Lapatinib + Capecitabine) was estimated by Cox regression.
16.Secondary Outcome
Title Percentage of Participants With Symptom Progression
Hide Description Symptom progression was defined as the documentation of a >/= 5-point decrease from baseline in the scoring of responses as measured by the Functional Assessment of Cancer Therapy-for participants with Breast Cancer (FACT-B) questionnaire with the Trial Outcomes Index-Physical/Functional/Breast (TOI-PFB) subscale. The FACT-B TOI-PFB subscale contained 24 items from 3 subsections of the FACT-B questionnaire: Physical well-being, functional well-being, and additional concerns for breast cancer participants (breast cancer subscale [BCS]). All items in the questionnaire were rated by the participant on a 5-point scale ranging from 0 ("not at all") to 4 ("very much"). The total score ranged from 0 to 96 with higher score indicating better perceived quality of life. The percentage of participants with symptom progression was reported.
Time Frame From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants on the basis of the treatment assigned at randomization. Only female participants with a Baseline assessment and at least 1 follow-up assessment were included in the analysis.
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine
Hide Arm/Group Description:
Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
Overall Number of Participants Analyzed 450 445
Measure Type: Number
Unit of Measure: percentage of participants
54.7 57.8
17.Secondary Outcome
Title Time to Symptom Progression
Hide Description Time to symptom progression was defined as the time from randomization to the first documentation of a >/= 5-point decrease from baseline in the scoring of responses as measured by the FACT-B questionnaire with the TOI-PFB subscale. The FACT-B TOI-PFB subscale contained 24 items from 3 subsections of the FACT-B questionnaire: Physical well-being, functional well-being, and additional concerns for breast cancer participants (BCS). All items in the questionnaire were rated by the participant on a 5-point scale ranging from 0 ("not at all") to 4 ("very much"). The total score ranged from 0 to 96 with higher score indicating better perceived quality of life. The median time to symptom progression was estimated using Kaplan-Meier method. The 95% CI was computed using the method of Brookmeyer and Crowley.
Time Frame From the date of randomization through the data cut-off date of 14 Jan 2012 (up to 2 years, 11 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants on the basis of the treatment assigned at randomization. Only female participants with a Baseline assessment and at least 1 follow-up assessment were included in the analysis.
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine
Hide Arm/Group Description:
Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
Overall Number of Participants Analyzed 450 445
Median (95% Confidence Interval)
Unit of Measure: Months
7.1
(5.59 to 8.44)
4.6
(4.14 to 5.78)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine, Lapatinib + Capecitabine
Comments Analysis stratified by region of enrollment, number of prior chemotherapeutic regimens (0-1 or >1), and visceral/ non-visceral disease.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0121
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.796
Confidence Interval (2-Sided) 95%
0.667 to 0.951
Estimation Comments HR (relative to Lapatinib + Capecitabine) was estimated by Cox regression.
Time Frame Only study-related serious adverse events (SAEs) were reported from randomization to first treatment; all SAEs and non-SAEs were reported from start of treatment until 30 days after treatment; and thereafter only treatment related SAEs were reported until data cut-off date of 21-Sep-2015 (up to 6 years and 7 months). For participants who crossed over from lapatinib + capecitabine to trastuzumab emtansine, data is reported from time of cross-over until 21-Sep-2015 (up to 3 years and 2 months).
Adverse Event Reporting Description Safety population included participants who received at least 1 dose of study medication. Safety analyses were based on the actual treatment received.
 
Arm/Group Title Trastuzumab Emtansine Lapatinib + Capecitabine Lapatinib + Capecitabine/ Trastuzumab Emtansine
Hide Arm/Group Description Participants received trastuzumab emtansine 3.6 mg/kg IV infusion over 30-90 minutes on Day 1 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants received lapatinib 1250 mg (five 250 mg tablets) orally once daily during each 21-day cycle + capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination. Participants of this group were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis. Participants of "Lapatinib + Capecitabine" arm were allowed to cross over to receive trastuzumab emtansine based on statistically significant OS benefit in favor of trastuzumab emtansine demonstrated in second interim analysis.
All-Cause Mortality
Trastuzumab Emtansine Lapatinib + Capecitabine Lapatinib + Capecitabine/ Trastuzumab Emtansine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Trastuzumab Emtansine Lapatinib + Capecitabine Lapatinib + Capecitabine/ Trastuzumab Emtansine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   92/490 (18.78%)   99/488 (20.29%)   19/136 (13.97%) 
Blood and lymphatic system disorders       
Anaemia * 1  1/490 (0.20%)  1/488 (0.20%)  0/136 (0.00%) 
Anaemia of malignant disease * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Febrile neutropenia * 1  0/490 (0.00%)  2/488 (0.41%)  0/136 (0.00%) 
Neutropenia * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Thrombocytopenia * 1  4/490 (0.82%)  1/488 (0.20%)  1/136 (0.74%) 
Cardiac disorders       
Angina pectoris * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Atrial fibrillation * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Cardiomyopathy * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Coronary artery disease * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Pericardial effusion * 1  0/490 (0.00%)  2/488 (0.41%)  0/136 (0.00%) 
Pericarditis * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Supraventricular tachycardia * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Tachycardia * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Ear and labyrinth disorders       
Vertigo * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Eye disorders       
Macular hole * 1  0/490 (0.00%)  0/488 (0.00%)  1/136 (0.74%) 
Gastrointestinal disorders       
Abdominal pain * 1  4/490 (0.82%)  3/488 (0.61%)  0/136 (0.00%) 
Ascites * 1  0/490 (0.00%)  0/488 (0.00%)  1/136 (0.74%) 
Colitis * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Constipation * 1  1/490 (0.20%)  1/488 (0.20%)  0/136 (0.00%) 
Diarrhoea * 1  3/490 (0.61%)  17/488 (3.48%)  0/136 (0.00%) 
Enteritis * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Fistula of small intestine * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Gastric haemorrhage * 1  0/490 (0.00%)  0/488 (0.00%)  1/136 (0.74%) 
Gastric ulcer * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Gastritis * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Gastrointestinal haemorrhage * 1  2/490 (0.41%)  0/488 (0.00%)  0/136 (0.00%) 
Gastrointestinal obstruction * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Ileus * 1  0/490 (0.00%)  2/488 (0.41%)  0/136 (0.00%) 
Intestinal haemorrhage * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Intestinal obstruction * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Nausea * 1  2/490 (0.41%)  3/488 (0.61%)  0/136 (0.00%) 
Peptic ulcer haemorrhage * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Upper gastrointestinal haemorrhage * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Vomiting * 1  7/490 (1.43%)  10/488 (2.05%)  0/136 (0.00%) 
General disorders       
Malaise * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Asthenia * 1  1/490 (0.20%)  2/488 (0.41%)  1/136 (0.74%) 
Chest pain * 1  2/490 (0.41%)  0/488 (0.00%)  0/136 (0.00%) 
Fatigue * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Mucosal inflammation * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Multi-organ failure * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Oedema peripheral * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Pain * 1  2/490 (0.41%)  1/488 (0.20%)  0/136 (0.00%) 
Pyrexia * 1  8/490 (1.63%)  3/488 (0.61%)  2/136 (1.47%) 
Hepatobiliary disorders       
Cholangitis * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Cholangitis acute * 1  0/490 (0.00%)  0/488 (0.00%)  1/136 (0.74%) 
Cholestasis * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Hepatitis toxic * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Hepatotoxicity * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Hyperbilirubinaemia * 1  0/490 (0.00%)  2/488 (0.41%)  0/136 (0.00%) 
Nodular regenerative hyperplasia * 1  0/490 (0.00%)  0/488 (0.00%)  1/136 (0.74%) 
Portal hypertension * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Immune system disorders       
Hypersensitivity * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Infections and infestations       
Unmapped (Bacteremia due to infected port) * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Appendicitis * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Bacteraemia * 1  1/490 (0.20%)  1/488 (0.20%)  0/136 (0.00%) 
Bronchitis * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Catheter site infection * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Cellulitis * 1  2/490 (0.41%)  3/488 (0.61%)  1/136 (0.74%) 
Clostridium difficile colitis * 1  1/490 (0.20%)  1/488 (0.20%)  0/136 (0.00%) 
Device related infection * 1  2/490 (0.41%)  0/488 (0.00%)  0/136 (0.00%) 
Enterococcal infection * 1  1/490 (0.20%)  0/488 (0.00%)  1/136 (0.74%) 
Erysipelas * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Gastroenteritis norovirus * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
H1N1 influenza * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Herpes zoster * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Infection * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Listeriosis * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Lower respiratory tract infection * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Nasopharyngitis * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Neutropenic sepsis * 1  2/490 (0.41%)  0/488 (0.00%)  0/136 (0.00%) 
Parotitis * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Pneumocystis jirovecii pneumonia * 1  0/490 (0.00%)  0/488 (0.00%)  1/136 (0.74%) 
Pneumonia * 1  4/490 (0.82%)  1/488 (0.20%)  1/136 (0.74%) 
Pneumonia bacterial * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Post procedural infection * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Pyelonephritis acute * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Respiratory tract infection * 1  0/490 (0.00%)  0/488 (0.00%)  2/136 (1.47%) 
Salmonellosis * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Sepsis * 1  1/490 (0.20%)  1/488 (0.20%)  0/136 (0.00%) 
Staphylococcal sepsis * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Tooth infection * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Upper respiratory tract infection * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Urinary tract infection * 1  3/490 (0.61%)  0/488 (0.00%)  1/136 (0.74%) 
Urosepsis * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Injury, poisoning and procedural complications       
Ankle fracture * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Delayed haemolytic transfusion reaction * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Extradural haematoma * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Fall * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Femoral neck fracture * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Femur fracture * 1  3/490 (0.61%)  2/488 (0.41%)  0/136 (0.00%) 
Fibula fracture * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Hip fracture * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Infusion related reaction * 1  1/490 (0.20%)  0/488 (0.00%)  1/136 (0.74%) 
Subdural haemorrhage * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Synovial rupture * 1  0/490 (0.00%)  0/488 (0.00%)  1/136 (0.74%) 
Wound * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Wound secretion * 1  0/490 (0.00%)  0/488 (0.00%)  1/136 (0.74%) 
Wrist fracture * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Investigations       
Alanine aminotransferase increased * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Blood bilirubin increased * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Gamma-glutamyltransferase increased * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Haemoglobin decreased * 1  0/490 (0.00%)  0/488 (0.00%)  1/136 (0.74%) 
Metabolism and nutrition disorders       
Dehydration * 1  0/490 (0.00%)  2/488 (0.41%)  0/136 (0.00%) 
Failure to thrive * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Hypercalcaemia * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Hypokalaemia * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Hyponatraemia * 1  2/490 (0.41%)  1/488 (0.20%)  0/136 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain * 1  3/490 (0.61%)  0/488 (0.00%)  0/136 (0.00%) 
Bone pain * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Muscular weakness * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Osteonecrosis of jaw * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Pain in extremity * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Pathological fracture * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Spinal column stenosis * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Spondylitis * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Acute myeloid leukaemia * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Breast cancer * 1  0/490 (0.00%)  0/488 (0.00%)  1/136 (0.74%) 
Infected neoplasm * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Lentigo maligna * 1  0/490 (0.00%)  0/488 (0.00%)  1/136 (0.74%) 
Myelodysplastic syndrome * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Second primary malignancy * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Squamous cell carcinoma * 1  0/490 (0.00%)  0/488 (0.00%)  1/136 (0.74%) 
Uterine cancer * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Nervous system disorders       
Cerebrovascular accident * 1  1/490 (0.20%)  1/488 (0.20%)  0/136 (0.00%) 
Coma * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Dizziness * 1  2/490 (0.41%)  2/488 (0.41%)  0/136 (0.00%) 
Epilepsy * 1  1/490 (0.20%)  1/488 (0.20%)  0/136 (0.00%) 
Headache * 1  1/490 (0.20%)  2/488 (0.41%)  0/136 (0.00%) 
Hemiplegia * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Hydrocephalus * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Metabolic encephalopathy * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Parkinson's disease * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Status epilepticus * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Syncope * 1  0/490 (0.00%)  2/488 (0.41%)  0/136 (0.00%) 
Psychiatric disorders       
Agitation * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Confusional state * 1  1/490 (0.20%)  1/488 (0.20%)  0/136 (0.00%) 
Depression * 1  0/490 (0.00%)  2/488 (0.41%)  0/136 (0.00%) 
Substance-induced psychotic disorder * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Renal and urinary disorders       
Dysuria * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Renal failure * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Ureteric obstruction * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Urinary tract obstruction * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Reproductive system and breast disorders       
Menometrorrhagia * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Metrorrhagia * 1  2/490 (0.41%)  1/488 (0.20%)  0/136 (0.00%) 
Ovarian cyst * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Uterine haemorrhage * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Acute respiratory distress syndrome * 1  1/490 (0.20%)  2/488 (0.41%)  0/136 (0.00%) 
Alveolitis allergic * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Asthma * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Dyspnoea * 1  2/490 (0.41%)  0/488 (0.00%)  0/136 (0.00%) 
Epistaxis * 1  1/490 (0.20%)  0/488 (0.00%)  1/136 (0.74%) 
Haemoptysis * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Hypoxia * 1  1/490 (0.20%)  0/488 (0.00%)  1/136 (0.74%) 
Pleural effusion * 1  1/490 (0.20%)  1/488 (0.20%)  0/136 (0.00%) 
Pleuritic pain * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Pneumonitis * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Pneumothorax * 1  0/490 (0.00%)  0/488 (0.00%)  1/136 (0.74%) 
Pulmonary embolism * 1  0/490 (0.00%)  9/488 (1.84%)  0/136 (0.00%) 
Pulmonary oedema * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Respiratory failure * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Skin and subcutaneous tissue disorders       
Dermatitis contact * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Rash * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Skin haemorrhage * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Urticaria * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
Surgical and medical procedures       
Abortion induced * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Vascular disorders       
Deep vein thrombosis * 1  0/490 (0.00%)  2/488 (0.41%)  0/136 (0.00%) 
Labile blood pressure * 1  1/490 (0.20%)  0/488 (0.00%)  0/136 (0.00%) 
Thrombosis * 1  0/490 (0.00%)  2/488 (0.41%)  0/136 (0.00%) 
Venous thrombosis * 1  0/490 (0.00%)  1/488 (0.20%)  0/136 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Trastuzumab Emtansine Lapatinib + Capecitabine Lapatinib + Capecitabine/ Trastuzumab Emtansine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   474/490 (96.73%)   471/488 (96.52%)   115/136 (84.56%) 
Blood and lymphatic system disorders       
Anaemia * 1  67/490 (13.67%)  40/488 (8.20%)  11/136 (8.09%) 
Neutropenia * 1  37/490 (7.55%)  43/488 (8.81%)  0/136 (0.00%) 
Thrombocytopenia * 1  150/490 (30.61%)  13/488 (2.66%)  23/136 (16.91%) 
Eye disorders       
Dry eye * 1  0/490 (0.00%)  0/488 (0.00%)  7/136 (5.15%) 
Gastrointestinal disorders       
Abdominal pain * 1  43/490 (8.78%)  50/488 (10.25%)  0/136 (0.00%) 
Abdominal pain upper * 1  60/490 (12.24%)  45/488 (9.22%)  0/136 (0.00%) 
Constipation * 1  139/490 (28.37%)  59/488 (12.09%)  22/136 (16.18%) 
Diarrhoea * 1  123/490 (25.10%)  385/488 (78.89%)  20/136 (14.71%) 
Dry mouth * 1  85/490 (17.35%)  26/488 (5.33%)  20/136 (14.71%) 
Dyspepsia * 1  51/490 (10.41%)  57/488 (11.68%)  7/136 (5.15%) 
Gingival bleeding * 1  0/490 (0.00%)  0/488 (0.00%)  8/136 (5.88%) 
Nausea * 1  202/490 (41.22%)  224/488 (45.90%)  35/136 (25.74%) 
Stomatitis * 1  20/490 (4.08%)  70/488 (14.34%)  0/136 (0.00%) 
Vomiting * 1  98/490 (20.00%)  145/488 (29.71%)  13/136 (9.56%) 
General disorders       
Influenza like illness * 1  26/490 (5.31%)  9/488 (1.84%)  13/136 (9.56%) 
Asthenia * 1  91/490 (18.57%)  86/488 (17.62%)  23/136 (16.91%) 
Chest pain * 1  40/490 (8.16%)  27/488 (5.53%)  0/136 (0.00%) 
Chills * 1  42/490 (8.57%)  16/488 (3.28%)  13/136 (9.56%) 
Fatigue * 1  180/490 (36.73%)  145/488 (29.71%)  30/136 (22.06%) 
Mucosal inflammation * 1  33/490 (6.73%)  93/488 (19.06%)  0/136 (0.00%) 
Oedema peripheral * 1  38/490 (7.76%)  38/488 (7.79%)  10/136 (7.35%) 
Pain * 1  35/490 (7.14%)  14/488 (2.87%)  0/136 (0.00%) 
Pyrexia * 1  95/490 (19.39%)  43/488 (8.81%)  18/136 (13.24%) 
Hepatobiliary disorders       
Hyperbilirubinaemia * 1  13/490 (2.65%)  46/488 (9.43%)  0/136 (0.00%) 
Infections and infestations       
Nasopharyngitis * 1  50/490 (10.20%)  41/488 (8.40%)  14/136 (10.29%) 
Paronychia * 1  2/490 (0.41%)  59/488 (12.09%)  0/136 (0.00%) 
Upper respiratory tract infection * 1  56/490 (11.43%)  40/488 (8.20%)  14/136 (10.29%) 
Urinary tract infection * 1  52/490 (10.61%)  21/488 (4.30%)  0/136 (0.00%) 
Injury, poisoning and procedural complications       
Infusion related reaction * 1  0/490 (0.00%)  0/488 (0.00%)  8/136 (5.88%) 
Investigations       
Alanine aminotransferase increased * 1  92/490 (18.78%)  48/488 (9.84%)  14/136 (10.29%) 
Aspartate aminotransferase increased * 1  123/490 (25.10%)  53/488 (10.86%)  25/136 (18.38%) 
Blood alkaline phosphatase increased * 1  26/490 (5.31%)  23/488 (4.71%)  9/136 (6.62%) 
Blood bilirubin increased * 1  21/490 (4.29%)  32/488 (6.56%)  11/136 (8.09%) 
Platelet count decreased * 1  0/490 (0.00%)  0/488 (0.00%)  8/136 (5.88%) 
Weight decreased * 1  38/490 (7.76%)  37/488 (7.58%)  7/136 (5.15%) 
Metabolism and nutrition disorders       
Decreased appetite * 1  105/490 (21.43%)  117/488 (23.98%)  21/136 (15.44%) 
Dehydration * 1  9/490 (1.84%)  25/488 (5.12%)  0/136 (0.00%) 
Hypokalaemia * 1  47/490 (9.59%)  45/488 (9.22%)  7/136 (5.15%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  102/490 (20.82%)  46/488 (9.43%)  21/136 (15.44%) 
Back pain * 1  78/490 (15.92%)  63/488 (12.91%)  9/136 (6.62%) 
Bone pain * 1  34/490 (6.94%)  20/488 (4.10%)  0/136 (0.00%) 
Muscle spasms * 1  39/490 (7.96%)  22/488 (4.51%)  8/136 (5.88%) 
Musculoskeletal pain * 1  46/490 (9.39%)  22/488 (4.51%)  10/136 (7.35%) 
Myalgia * 1  70/490 (14.29%)  20/488 (4.10%)  16/136 (11.76%) 
Pain in extremity * 1  71/490 (14.49%)  61/488 (12.50%)  8/136 (5.88%) 
Nervous system disorders       
Dizziness * 1  62/490 (12.65%)  50/488 (10.25%)  0/136 (0.00%) 
Dysgeusia * 1  41/490 (8.37%)  21/488 (4.30%)  0/136 (0.00%) 
Headache * 1  146/490 (29.80%)  77/488 (15.78%)  28/136 (20.59%) 
Neuropathy peripheral * 1  59/490 (12.04%)  30/488 (6.15%)  16/136 (11.76%) 
Paraesthesia * 1  31/490 (6.33%)  20/488 (4.10%)  7/136 (5.15%) 
Peripheral sensory neuropathy * 1  36/490 (7.35%)  27/488 (5.53%)  0/136 (0.00%) 
Psychiatric disorders       
Anxiety * 1  31/490 (6.33%)  15/488 (3.07%)  0/136 (0.00%) 
Depression * 1  27/490 (5.51%)  30/488 (6.15%)  0/136 (0.00%) 
Insomnia * 1  69/490 (14.08%)  45/488 (9.22%)  14/136 (10.29%) 
Respiratory, thoracic and mediastinal disorders       
Cough * 1  100/490 (20.41%)  68/488 (13.93%)  18/136 (13.24%) 
Dyspnoea * 1  61/490 (12.45%)  41/488 (8.40%)  17/136 (12.50%) 
Epistaxis * 1  121/490 (24.69%)  44/488 (9.02%)  35/136 (25.74%) 
Oropharyngeal pain * 1  24/490 (4.90%)  26/488 (5.33%)  0/136 (0.00%) 
Rhinorrhoea * 1  0/490 (0.00%)  0/488 (0.00%)  11/136 (8.09%) 
Skin and subcutaneous tissue disorders       
Alopecia * 1  19/490 (3.88%)  25/488 (5.12%)  0/136 (0.00%) 
Dermatitis acneiform * 1  3/490 (0.61%)  28/488 (5.74%)  0/136 (0.00%) 
Dry skin * 1  17/490 (3.47%)  54/488 (11.07%)  8/136 (5.88%) 
Erythema * 1  16/490 (3.27%)  25/488 (5.12%)  0/136 (0.00%) 
Nail disorder * 1  18/490 (3.67%)  48/488 (9.84%)  0/136 (0.00%) 
Palmar-Plantar erythrodysaesthesia syndrome * 1  7/490 (1.43%)  291/488 (59.63%)  7/136 (5.15%) 
Pruritus * 1  32/490 (6.53%)  46/488 (9.43%)  7/136 (5.15%) 
Rash * 1  64/490 (13.06%)  133/488 (27.25%)  17/136 (12.50%) 
Skin fissures * 1  2/490 (0.41%)  27/488 (5.53%)  0/136 (0.00%) 
Skin hyperpigmentation * 1  2/490 (0.41%)  25/488 (5.12%)  0/136 (0.00%) 
Vascular disorders       
Hypertension * 1  29/490 (5.92%)  11/488 (2.25%)  7/136 (5.15%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.1
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00829166    
Other Study ID Numbers: BO21977
TDM4370g ( Other Identifier: Genentech )
First Submitted: January 22, 2009
First Posted: January 26, 2009
Results First Submitted: February 22, 2013
Results First Posted: April 23, 2013
Last Update Posted: October 31, 2016