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A Study of Trastuzumab Emtansine in Comparison With Treatment of Physician's Choice in Participants With HER2-positive Breast Cancer Who Have Received at Least Two Prior Regimens of HER2-directed Therapy (TH3RESA)

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ClinicalTrials.gov Identifier: NCT01419197
Recruitment Status : Completed
First Posted : August 18, 2011
Results First Posted : May 5, 2014
Last Update Posted : October 12, 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: Treatment of physician's choice
Enrollment 602

Recruitment Details  
Pre-assignment Details A total of 602 patients were randomized to the study (404 to receive Trastuzumab Emtansine and 198 to receive Treatment of Physician’s Choice).
Arm/Group Title Trastuzumab Emtansine Treatment of Physician’s Choice
Hide Arm/Group Description Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity. Treatment of physician’s choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and human epidermal growth factor receptor 2 (HER2)-directed therapy.
Period Title: Overall Study
Started 404 198
Switched to Trastuzumab Emtansine 0 94
Completed 0 0
Not Completed 404 198
Reason Not Completed
Death             247             122
Physician Decision             4             4
Non-compliance             3             1
Withdrawal by Subject             33             32
Study Completed by Sponsor             103             34
Reason Not Specified             0             1
Lost to Follow-up             14             4
Arm/Group Title Trastuzumab Emtansine Treatment of Physician’s Choice Total
Hide Arm/Group Description Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity. Treatment of physician’s choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy. Total of all reporting groups
Overall Number of Baseline Participants 404 198 602
Hide Baseline Analysis Population Description
Randomized population: All participants who were randomized to the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 404 participants 198 participants 602 participants
53.3  (10.4) 54.3  (10.8) 53.6  (10.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 404 participants 198 participants 602 participants
Female
401
  99.3%
197
  99.5%
598
  99.3%
Male
3
   0.7%
1
   0.5%
4
   0.7%
1.Primary Outcome
Title Progression-free Survival
Hide Description Progression-free survival was defined as the time from randomization to the first documented disease progression by investigator assessment using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death from any cause, whichever occurred first. Progression-free survival was a co-primary endpoint.
Time Frame Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Trastuzumab Emtansine Treatment of Physician’s Choice
Hide Arm/Group Description:
Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
Treatment of physician’s choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Overall Number of Participants Analyzed 404 198
Median (95% Confidence Interval)
Unit of Measure: Months
6.2
(5.59 to 6.87)
3.3
(2.89 to 4.14)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine, Treatment of Physician’s Choice
Comments The analysis was stratified for 1) World region (United States, Western Europe, or Other); 2) Number of prior regimens, excluding single-agent hormones, for treatment of metastatic or unresectable locally advanced/recurrent disease (≤ 3 or > 3); and 3) Presence of visceral disease (any visceral disease vs no visceral disease).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The two-sided stratified log-rank test was used to compare progression-free survival between the two treatment arms at the overall two-sided significance level of 0.5%.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.528
Confidence Interval (2-Sided) 95%
0.422 to 0.661
Estimation Comments The hazard ratio was estimated by Cox regression.
2.Primary Outcome
Title Overall Survival
Hide Description Overall survival (OS) was defined as the time from randomization to death from any cause. Overall survival was a co-primary endpoint.
Time Frame Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Trastuzumab Emtansine Treatment of Physician’s Choice
Hide Arm/Group Description:
Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
Treatment of physician’s choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Overall Number of Participants Analyzed 404 198
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(13.14 to NA)
14.9 [2] 
(11.27 to NA)
[1]
The median and the upper limit of the confidence interval could not be estimated due to too few events.
[2]
The upper limit of the confidence interval could not be estimated due to too few events.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine, Treatment of Physician’s Choice
Comments The analysis was stratified for 1) World region (United States, Western Europe, or Other); 2) Number of prior regimens, excluding single-agent hormones, for treatment of metastatic or unresectable locally advanced/recurrent disease (≤ 3 or > 3); and 3) Presence of visceral disease (any visceral disease vs no visceral disease).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0034
Comments The 2-sided stratified log-rank test was used at the overall two-sided significance level of 4.5%. The pre-specified O’Brien-Fleming stopping boundary for this first OS interim analysis was HR<0.363 (p-value < 0.0000013).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.552
Confidence Interval (2-Sided) 95%
0.369 to 0.826
Estimation Comments The hazard ratio was estimated by Cox regression.
3.Secondary Outcome
Title Percentage of Participants With an Objective Response
Hide Description An objective response was defined as a complete or partial response determined on 2 consecutive occasions ≥ 4 weeks apart using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must be < 10 mm on the short axis. Partial response was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum. Participants who had no post-baseline tumor assessment were counted as non-responders.
Time Frame Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized population: All participants who were randomized to the study. Only participants with measurable disease at Baseline were included in the analysis. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Trastuzumab Emtansine Treatment of Physician’s Choice
Hide Arm/Group Description:
Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
Treatment of physician’s choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Overall Number of Participants Analyzed 345 163
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
31.3
(26.5 to 36.5)
8.6
(5.1 to 13.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine, Treatment of Physician’s Choice
Comments The analysis was stratified for 1) World region (United States, Western Europe, or Other); 2) Number of prior regimens, excluding single-agent hormones, for treatment of metastatic or unresectable locally advanced/recurrent disease (≤ 3 or > 3); and 3) Presence of visceral disease (any visceral disease vs no visceral disease).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Percentage
Estimated Value 22.7
Confidence Interval (2-Sided) 95%
16.2 to 29.2
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Duration of the Objective Response
Hide Description Duration of the objective response was defined as the time from the first tumor assessment that was judged to indicate that the patient had an objective response to the time of first documented disease progression using RECIST v1.1 per investigator assessment or death from any cause, whichever occurred first.
Time Frame Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized population: All participants who were randomized to the study. Only participants with an objective response were included in the analysis. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Trastuzumab Emtansine Treatment of Physician’s Choice
Hide Arm/Group Description:
Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
Treatment of physician’s choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Overall Number of Participants Analyzed 108 14
Median (95% Confidence Interval)
Unit of Measure: Months
9.7
(6.60 to 10.51)
NA [1] 
(2.40 to NA)
[1]
The median and the upper confidence interval value could not be estimated due to too few events.
5.Secondary Outcome
Title 6-month and 1-year Survival
Hide Description 6-month and 1-year survival were defined as the percentage of participants who were alive at 6 months and 1 year, respectively, as estimated using Kaplan-Meier method.
Time Frame Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Trastuzumab Emtansine Treatment of Physician’s Choice
Hide Arm/Group Description:
Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
Treatment of physician’s choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Overall Number of Participants Analyzed 404 198
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
6-Month Survival
90.9
(87.79 to 94.01)
78.3
(71.49 to 85.19)
1-Year Survival
68.6
(59.91 to 77.28)
56.9
(42.22 to 71.63)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine, Treatment of Physician’s Choice
Comments 6-month survival
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments The p-value for the difference in survival rate was derived from the z-test using the standard errors computed using Greenwood`s method.
Method z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Survival Percentage
Estimated Value 12.6
Confidence Interval (2-Sided) 95%
5.03 to 20.09
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine, Treatment of Physician’s Choice
Comments 1-year survival
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1805
Comments The p-value for the difference in survival rates was derived from the z-test using the standard errors computed using Greenwood`s method.
Method z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Survival Percentage
Estimated Value 11.7
Confidence Interval (2-Sided) 95%
-5.41 to 28.75
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Time to Pain Symptom Progression
Hide Description Time to pain symptom progression was defined as the time from randomization to the first documentation of an increase in narcotic use and/or a 10 point increase from Baseline in the pain score as measured by the European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire for patients with bone metastases (EORTC QLQ-BM22). The EORTC QLQ-BM22 assesses the symptoms of bone metastases using 22 items: 5 items for sites of pain, 3 pain characteristics, 8 functional interference aspects, and 6 psychosocial aspects. The pain score was derived from the 3 pain characteristic items. Each item was rated on a 4-point scale, where 1=Not at all to 4=Very much. The pain score was the sum of the 3 pain characteristic scores and was normalized to a scale of 0 to 100. A higher score indicates greater pain.
Time Frame Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized population: All participants who were randomized to the study. Only participants with a Baseline pain score and at least 1 post-baseline pain score were included in the analysis. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Trastuzumab Emtansine Treatment of Physician’s Choice
Hide Arm/Group Description:
Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
Treatment of physician’s choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Overall Number of Participants Analyzed 297 117
Median (95% Confidence Interval)
Unit of Measure: Months
2.9
(2.2 to 3.7)
3.6
(2.7 to 4.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine, Treatment of Physician’s Choice
Comments The analysis was stratified for 1) World region (United States, Western Europe, or Other); 2) Number of prior regimens, excluding single-agent hormones, for treatment of metastatic or unresectable locally advanced/recurrent disease (≤ 3 or > 3); and 3) Presence of visceral disease (any visceral disease vs no visceral disease).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4952
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.115
Confidence Interval (2-Sided) 95%
0.819 to 1.517
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle
Hide Description The EORTC QLQ-BM22 assesses the symptoms of bone metastases using 22 items: 5 items for sites of pain, 3 pain characteristics, 8 functional interference aspects, and 6 psychosocial aspects. The pain score was derived from the 3 pain characteristic items. Each item was rated on a 4-point scale, where 1=Not at all to 4=Very much. The pain score was the sum of the 3 pain characteristic scores and was normalized to a scale of 0 to 100. A higher score indicates greater pain. A negative change score indicates improvement.
Time Frame Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized population: All participants who were randomized to the study. Only participants with a Baseline pain score and at least 1 post-baseline pain score were included in the analysis. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Trastuzumab Emtansine Treatment of Physician’s Choice
Hide Arm/Group Description:
Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
Treatment of physician’s choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Overall Number of Participants Analyzed 297 117
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Cycle 2 (n=282,98) -3.4  (21.1) -9.4  (22.1)
Cycle 3 (n=257,86) -4.6  (21.1) -6.1  (21.4)
Cycle 4 (n=236,74) -4.8  (19.6) -3.8  (24.1)
Cycle 5 (n=224,54) -6.6  (22.8) -2.7  (18.9)
Cycle 6 (n=195,42) -4.8  (23.5) 2.4  (17.1)
Cycle 7 (n=163,30) -4.2  (23.8) -1.5  (15.6)
Cycle 8 (n=130,20) -7.0  (21.0) 2.2  (18.6)
Cycle 9 (n=97,15) -5.8  (22.2) 6.7  (20.1)
Cycle 10 (n=80,7) -8.9  (21.2) 1.6  (11.9)
Cycle 11 (n=56,8) -10.5  (23.1) 0.0  (8.4)
Cycle 12 (n=48,7) -11.3  (25.8) 1.6  (7.7)
Cycle 13 (n=40,5) -10.0  (23.3) 2.2  (12.2)
Cycle 14 (n=33,5) -10.1  (21.8) 0.0  (7.9)
Cycle 15 (n=27,3) -13.2  (22.0) 0.0  (0.0)
Cycle 16 (n=19,3) -12.3  (19.6) -3.7  (6.4)
Cycle 17 (n=15,2) -7.4  (22.9) -5.6  (7.9)
Cycle 18 (n=11,0) -9.1  (12.0) NA [1]   (NA)
Cycle 19 (n=8,0) 1.4  (9.3) NA [1]   (NA)
Cycle 20 (n=4,0) -5.6  (23.1) NA [1]   (NA)
Cycle 21 (n=3,0) -3.7  (6.4) NA [1]   (NA)
Termination Visit (n=84,37) -1.6  (21.8) -9.0  (23.3)
[1]
There were no participants with available data.
8.Secondary Outcome
Title Overall Survival (Final Analysis)
Hide Description Overall survival was defined as the time from randomization to death from any cause.
Time Frame Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Trastuzumab Emtansine Treatment of Physician’s Choice
Hide Arm/Group Description:
Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
Treatment of physician’s choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Overall Number of Participants Analyzed 404 198
Median (95% Confidence Interval)
Unit of Measure: Months
22.7
(19.35 to 27.47)
15.8
(13.50 to 18.66)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine, Treatment of Physician’s Choice
Comments The analysis was stratified for 1) World region (United States, Western Europe, or Other); 2) Number of prior regimens, excluding single-agent hormones, for treatment of metastatic or unresectable locally advanced/recurrent disease (≤ 3 or > 3); and 3) Presence of visceral disease (any visceral disease versus no visceral disease).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments The two-sided stratified log-rank test was used at the overall two-sided significance level of 4.5%. The pre-specified O’Brien-Fleming stopping boundary for this second and final interim analysis was HR<0.748 (p value < 0.012).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.677
Confidence Interval (2-Sided) 95%
0.539 to 0.850
Estimation Comments The hazard ratio was estimated by Cox regression.
9.Secondary Outcome
Title 6-month and 1-year Survival (Final Analysis)
Hide Description 6-month and 1-year survival were defined as the percentage of participants who were alive at 6 months and 1 year, respectively, as estimated using Kaplan-Meier method.
Time Frame Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.
Arm/Group Title Trastuzumab Emtansine Treatment of Physician’s Choice
Hide Arm/Group Description:
Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
Treatment of physician’s choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Overall Number of Participants Analyzed 404 198
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
6-Month Survival
91.3
(88.52 to 94.11)
78.9
(72.78 to 85.04)
1-Year Survival
76.5
(72.23 to 80.79)
65.6
(58.36 to 72.76)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine, Treatment of Physician’s Choice
Comments 6-month survival
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments The p-value for the difference in survival rate was derived from the z-test using the standard errors computed using Greenwood`s method.
Method z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Survival Percentage
Estimated Value 12.4
Confidence Interval (2-Sided) 95%
5.67 to 19.14
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine, Treatment of Physician’s Choice
Comments 1-year survival
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0104
Comments The p-value for the difference in survival rates was derived from the z-test using the standard errors computed using Greenwood`s method.
Method z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Survival Percentage
Estimated Value 11.0
Confidence Interval (2-Sided) 95%
2.58 to 19.33
Estimation Comments [Not Specified]
Time Frame Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years).
Adverse Event Reporting Description Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
 
Arm/Group Title Trastuzumab Emtansine Treatment of Physician’s Choice (TPC) Trastuzumab Emtansine - Post TPC Treatment Switch
Hide Arm/Group Description Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity. Treatment of physician’s choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy. Participants, who switched treatment in the Treatment of Physician's Choice arm to trastuzumab emtansine, were administered trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
All-Cause Mortality
Trastuzumab Emtansine Treatment of Physician’s Choice (TPC) Trastuzumab Emtansine - Post TPC Treatment Switch
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Trastuzumab Emtansine Treatment of Physician’s Choice (TPC) Trastuzumab Emtansine - Post TPC Treatment Switch
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   102/403 (25.31%)   41/184 (22.28%)   19/94 (20.21%) 
Blood and lymphatic system disorders       
Anaemia  1  1/403 (0.25%)  2/184 (1.09%)  1/94 (1.06%) 
Febrile neutropenia  1  1/403 (0.25%)  7/184 (3.80%)  0/94 (0.00%) 
Granulocytopenia  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Neutropenia  1  1/403 (0.25%)  2/184 (1.09%)  0/94 (0.00%) 
Thrombocytopenia  1  1/403 (0.25%)  1/184 (0.54%)  0/94 (0.00%) 
Cardiac disorders       
Cardiac failure  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Ear and labyrinth disorders       
Vertigo  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Endocrine disorders       
Hypercalcaemia of malignancy  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Eye disorders       
Vision blurred  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Gastrointestinal disorders       
Abdominal discomfort  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Abdominal pain  1  4/403 (0.99%)  3/184 (1.63%)  1/94 (1.06%) 
Abdominal pain upper  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Abdominal wall haematoma  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Colitis  1  2/403 (0.50%)  0/184 (0.00%)  0/94 (0.00%) 
Diarrhoea  1  2/403 (0.50%)  1/184 (0.54%)  0/94 (0.00%) 
Gastric haemorrhage  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Ileus  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Nausea  1  0/403 (0.00%)  2/184 (1.09%)  0/94 (0.00%) 
Obstruction gastric  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Pancreatitis  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Proctitis Haemorrhagic  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Small intestinal obstruction  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Upper gastrointestinal haemorrhage  1  0/403 (0.00%)  1/184 (0.54%)  1/94 (1.06%) 
Vomiting  1  2/403 (0.50%)  2/184 (1.09%)  0/94 (0.00%) 
General disorders       
Adverse drug reaction  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Asthenia  1  3/403 (0.74%)  0/184 (0.00%)  0/94 (0.00%) 
Death  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Device occlusion  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Fatigue  1  1/403 (0.25%)  1/184 (0.54%)  0/94 (0.00%) 
General physical health deterioration  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Malaise  1  2/403 (0.50%)  0/184 (0.00%)  0/94 (0.00%) 
Non-cardiac chest pain  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Oedema peripheral  1  2/403 (0.50%)  2/184 (1.09%)  0/94 (0.00%) 
Pain  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Pyrexia  1  7/403 (1.74%)  2/184 (1.09%)  1/94 (1.06%) 
Vessel puncture site haemorrhage  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Hepatobiliary disorders       
Bile duct obstruction  1  1/403 (0.25%)  1/184 (0.54%)  0/94 (0.00%) 
Cholangitis  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Cholecystitis  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Nodular regenerative hyperplasia  1  3/403 (0.74%)  0/184 (0.00%)  0/94 (0.00%) 
Hepatotoxicity  1  0/403 (0.00%)  0/184 (0.00%)  1/94 (1.06%) 
Immune system disorders       
Drug hypersensitivity  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Hypersensitivity  1  1/403 (0.25%)  0/184 (0.00%)  1/94 (1.06%) 
Infections and infestations       
Appendicitis  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Bronchopneumonia  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Cellulitis  1  2/403 (0.50%)  4/184 (2.17%)  1/94 (1.06%) 
Clostridium bacteraemia  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Device related infection  1  1/403 (0.25%)  1/184 (0.54%)  0/94 (0.00%) 
Device related sepsis  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Gastroenteritis  1  2/403 (0.50%)  0/184 (0.00%)  0/94 (0.00%) 
Infected fistula  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Infection  1  2/403 (0.50%)  0/184 (0.00%)  0/94 (0.00%) 
Infectious colitis  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Lung infection  1  1/403 (0.25%)  0/184 (0.00%)  1/94 (1.06%) 
Lymphangitis  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Mastitis  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Neutropenic sepsis  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Pharyngotonsillitis  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Pneumonia  1  5/403 (1.24%)  0/184 (0.00%)  1/94 (1.06%) 
Postoperative wound infection  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Sepsis  1  3/403 (0.74%)  0/184 (0.00%)  0/94 (0.00%) 
Sinusitis  1  1/403 (0.25%)  1/184 (0.54%)  0/94 (0.00%) 
Tracheitis  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Upper respiratory tract infection  1  2/403 (0.50%)  0/184 (0.00%)  0/94 (0.00%) 
Urinary tract infection  1  4/403 (0.99%)  0/184 (0.00%)  0/94 (0.00%) 
Urosepsis  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Viral upper respiratory tract infection  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Wound infection  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Abdominal infection  1  0/403 (0.00%)  0/184 (0.00%)  1/94 (1.06%) 
Abscess  1  0/403 (0.00%)  0/184 (0.00%)  1/94 (1.06%) 
Biliary tract infection  1  0/403 (0.00%)  0/184 (0.00%)  1/94 (1.06%) 
Injury, poisoning and procedural complications       
Fall  1  2/403 (0.50%)  0/184 (0.00%)  0/94 (0.00%) 
Femoral neck fracture  1  2/403 (0.50%)  0/184 (0.00%)  0/94 (0.00%) 
Femur fracture  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Infusion related reaction  1  1/403 (0.25%)  1/184 (0.54%)  0/94 (0.00%) 
Sternal fracture  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Subdural haematoma  1  2/403 (0.50%)  0/184 (0.00%)  0/94 (0.00%) 
Subdural haemorrhage  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Thoracic vertebral fracture  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Traumatic intracranial haemorrhage  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Wound decomposition  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Wound haemorrhage  1  1/403 (0.25%)  1/184 (0.54%)  0/94 (0.00%) 
Toxicity to various agents  1  0/403 (0.00%)  0/184 (0.00%)  1/94 (1.06%) 
Upper limb fracture  1  0/403 (0.00%)  0/184 (0.00%)  1/94 (1.06%) 
Investigations       
Transaminases increased  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
White blood cell count decreased  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  1/403 (0.25%)  0/184 (0.00%)  1/94 (1.06%) 
Dehydration  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Hypercalcaemia  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Hyperglycaemia  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Hypokalaemia  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Hyponatraemia  1  4/403 (0.99%)  0/184 (0.00%)  0/94 (0.00%) 
Hypophagia  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Malnutrition  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Back pain  1  2/403 (0.50%)  0/184 (0.00%)  0/94 (0.00%) 
Bone pain  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Muscle haemorrhage  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Musculoskeletal chest pain  1  1/403 (0.25%)  1/184 (0.54%)  0/94 (0.00%) 
Myalgia  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Spinal pain  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Muscular weakness  1  0/403 (0.00%)  0/184 (0.00%)  1/94 (1.06%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Rectal adenocarcinoma  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Tumour haemorrhage  1  2/403 (0.50%)  0/184 (0.00%)  0/94 (0.00%) 
Tumor pain  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Tumour necrosis  1  0/403 (0.00%)  0/184 (0.00%)  1/94 (1.06%) 
Nervous system disorders       
Ataxia  1  1/403 (0.25%)  1/184 (0.54%)  0/94 (0.00%) 
Brain oedema  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Cerebral haematoma  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Cerebral haemorrhage  1  2/403 (0.50%)  0/184 (0.00%)  0/94 (0.00%) 
Cognitive disorder  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Depressed level of consciousness  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Dizziness  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Haemorrhage intracranial  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Hepatic encephalopathy  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Loss of consciousness  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Paraesthesia  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Paraparesis  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Seizure  1  5/403 (1.24%)  0/184 (0.00%)  1/94 (1.06%) 
Somnolence  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Subarachnoid haemorrhage  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Transient ischaemic attack  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Visual field defect  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Epilepsy  1  0/403 (0.00%)  0/184 (0.00%)  1/94 (1.06%) 
Hemiplegia  1  0/403 (0.00%)  0/184 (0.00%)  1/94 (1.06%) 
Psychiatric disorders       
Confusional state  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Renal and urinary disorders       
Haematuria  1  1/403 (0.25%)  1/184 (0.54%)  0/94 (0.00%) 
Reproductive system and breast disorders       
Vaginal haemorrhage  1  2/403 (0.50%)  0/184 (0.00%)  0/94 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  6/403 (1.49%)  5/184 (2.72%)  2/94 (2.13%) 
Epistaxis  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Haemoptysis  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Non-cardiogenic pulmonary oedema  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Obliterative bronchiolitis  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Pleural effusion  1  3/403 (0.74%)  2/184 (1.09%)  0/94 (0.00%) 
Pleuritic pain  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Pneumonia aspiration  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Pneumonitis  1  2/403 (0.50%)  1/184 (0.54%)  0/94 (0.00%) 
Pneumothorax  1  1/403 (0.25%)  1/184 (0.54%)  0/94 (0.00%) 
Pulmonary embolism  1  1/403 (0.25%)  2/184 (1.09%)  1/94 (1.06%) 
Respiratory failure  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Pulmonary Fibrosis  1  0/403 (0.00%)  0/184 (0.00%)  1/94 (1.06%) 
Vascular disorders       
Deep vein thrombosis  1  2/403 (0.50%)  0/184 (0.00%)  0/94 (0.00%) 
Embolism  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Embolism venous  1  0/403 (0.00%)  1/184 (0.54%)  0/94 (0.00%) 
Hypertensive crisis  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Hypotension  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Lymphoedema  1  0/403 (0.00%)  1/184 (0.54%)  1/94 (1.06%) 
Superior vena cava syndrome  1  1/403 (0.25%)  0/184 (0.00%)  0/94 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Trastuzumab Emtansine Treatment of Physician’s Choice (TPC) Trastuzumab Emtansine - Post TPC Treatment Switch
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   371/403 (92.06%)   148/184 (80.43%)   74/94 (78.72%) 
Blood and lymphatic system disorders       
Anaemia  1  45/403 (11.17%)  19/184 (10.33%)  7/94 (7.45%) 
Leukopenia  1  9/403 (2.23%)  11/184 (5.98%)  0/94 (0.00%) 
Neutropenia  1  30/403 (7.44%)  39/184 (21.20%)  5/94 (5.32%) 
Thrombocytopenia  1  81/403 (20.10%)  6/184 (3.26%)  17/94 (18.09%) 
Eye disorders       
Lacrimation increased  1  0/403 (0.00%)  0/184 (0.00%)  5/94 (5.32%) 
Gastrointestinal disorders       
Abdominal pain  1  27/403 (6.70%)  20/184 (10.87%)  9/94 (9.57%) 
Constipation  1  90/403 (22.33%)  32/184 (17.39%)  7/94 (7.45%) 
Diarrhoea  1  52/403 (12.90%)  40/184 (21.74%)  10/94 (10.64%) 
Dry mouth  1  51/403 (12.66%)  2/184 (1.09%)  9/94 (9.57%) 
Dyspepsia  1  21/403 (5.21%)  12/184 (6.52%)  0/94 (0.00%) 
Gingival bleeding  1  21/403 (5.21%)  0/184 (0.00%)  0/94 (0.00%) 
Nausea  1  144/403 (35.73%)  40/184 (21.74%)  16/94 (17.02%) 
Stomatitis  1  13/403 (3.23%)  11/184 (5.98%)  0/94 (0.00%) 
Vomiting  1  77/403 (19.11%)  16/184 (8.70%)  10/94 (10.64%) 
Abdominal pain upper  1  0/403 (0.00%)  0/184 (0.00%)  7/94 (7.45%) 
General disorders       
Asthenia  1  76/403 (18.86%)  33/184 (17.93%)  15/94 (15.96%) 
Chills  1  21/403 (5.21%)  4/184 (2.17%)  0/94 (0.00%) 
Fatigue  1  123/403 (30.52%)  48/184 (26.09%)  10/94 (10.64%) 
Influenza like illness  1  21/403 (5.21%)  2/184 (1.09%)  0/94 (0.00%) 
Mucosal inflammation  1  17/403 (4.22%)  10/184 (5.43%)  7/94 (7.45%) 
Oedema peripheral  1  26/403 (6.45%)  11/184 (5.98%)  0/94 (0.00%) 
Pyrexia  1  77/403 (19.11%)  22/184 (11.96%)  14/94 (14.89%) 
Pain  1  0/403 (0.00%)  0/184 (0.00%)  5/94 (5.32%) 
Infections and infestations       
Nasopharyngitis  1  35/403 (8.68%)  12/184 (6.52%)  6/94 (6.38%) 
Upper respiratory tract infection  1  35/403 (8.68%)  8/184 (4.35%)  8/94 (8.51%) 
Urinary tract infection  1  26/403 (6.45%)  7/184 (3.80%)  9/94 (9.57%) 
Sinusitis  1  0/403 (0.00%)  0/184 (0.00%)  5/94 (5.32%) 
Investigations       
Alanine aminotransferase increased  1  38/403 (9.43%)  10/184 (5.43%)  7/94 (7.45%) 
Aspartate aminotransferase increased  1  51/403 (12.66%)  13/184 (7.07%)  13/94 (13.83%) 
Blood alkaline phosphatase increased  1  21/403 (5.21%)  5/184 (2.72%)  7/94 (7.45%) 
Blood bilirubin increased  1  38/403 (9.43%)  2/184 (1.09%)  5/94 (5.32%) 
Ejection fraction decreased  1  11/403 (2.73%)  12/184 (6.52%)  0/94 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  66/403 (16.38%)  25/184 (13.59%)  15/94 (15.96%) 
Hypokalaemia  1  30/403 (7.44%)  4/184 (2.17%)  6/94 (6.38%) 
Hyperglycaemia  1  0/403 (0.00%)  0/184 (0.00%)  5/94 (5.32%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  60/403 (14.89%)  8/184 (4.35%)  7/94 (7.45%) 
Back pain  1  35/403 (8.68%)  13/184 (7.07%)  6/94 (6.38%) 
Bone pain  1  22/403 (5.46%)  7/184 (3.80%)  0/94 (0.00%) 
Muscle spasms  1  26/403 (6.45%)  9/184 (4.89%)  0/94 (0.00%) 
Musculoskeletal pain  1  18/403 (4.47%)  10/184 (5.43%)  7/94 (7.45%) 
Myalgia  1  47/403 (11.66%)  14/184 (7.61%)  6/94 (6.38%) 
Pain in extremity  1  44/403 (10.92%)  9/184 (4.89%)  0/94 (0.00%) 
Nervous system disorders       
Dizziness  1  31/403 (7.69%)  6/184 (3.26%)  6/94 (6.38%) 
Headache  1  100/403 (24.81%)  22/184 (11.96%)  16/94 (17.02%) 
Neuropathy peripheral  1  20/403 (4.96%)  10/184 (5.43%)  7/94 (7.45%) 
Paraesthesia  1  28/403 (6.95%)  11/184 (5.98%)  9/94 (9.57%) 
Psychiatric disorders       
Insomnia  1  35/403 (8.68%)  6/184 (3.26%)  8/94 (8.51%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  76/403 (18.86%)  24/184 (13.04%)  12/94 (12.77%) 
Dyspnoea  1  42/403 (10.42%)  21/184 (11.41%)  6/94 (6.38%) 
Epistaxis  1  67/403 (16.63%)  7/184 (3.80%)  12/94 (12.77%) 
Skin and subcutaneous tissue disorders       
Alopecia  1  9/403 (2.23%)  20/184 (10.87%)  0/94 (0.00%) 
Pruritus  1  23/403 (5.71%)  17/184 (9.24%)  0/94 (0.00%) 
Rash  1  27/403 (6.70%)  19/184 (10.33%)  0/94 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.0)
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
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01419197     History of Changes
Other Study ID Numbers: TDM4997g
BO25734 ( Other Identifier: Hoffmann-La Roche )
2011-000509-29 ( EudraCT Number )
First Submitted: August 16, 2011
First Posted: August 18, 2011
Results First Submitted: February 7, 2014
Results First Posted: May 5, 2014
Last Update Posted: October 12, 2016