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A Study of Trastuzumab Emtansine Versus Taxane in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer

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ClinicalTrials.gov Identifier: NCT01641939
Recruitment Status : Terminated
First Posted : July 17, 2012
Results First Posted : August 11, 2016
Last Update Posted : May 12, 2017
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 Gastric Cancer
Interventions Drug: Taxane
Drug: trastuzumab emtansine
Enrollment 415
Recruitment Details  
Pre-assignment Details A total of 415 participants were randomized, of these 117 participants in taxane arm, 228 participants in 2.4 milligram per kilogram (mg/kg) trastuzumab emtansine arm, and 70 participants in 3.6 mg/kg trastuzumab emtansine arm received at least one dose of the treatment.
Arm/Group Title Standard Taxane Therapy Trastuzumab Emtansine 2.4 mg Trastuzumab Emtansine 3.6 mg
Hide Arm/Group Description Docetaxel was administered at 75 milligram per meter square (mg/m^2) intravenously (IV) on Day 1 of a 21-day cycle, or paclitaxel was administered at 80 mg/m^2 IV weekly (Days 1, 8, and 15 of a 21 day cycle) as per investigator's choice, until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue. Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue. Trastuzumab emtansine was administered on Days 1 of a 21-day cycle at 3.6 mg/kg IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Period Title: Overall Study
Started 117 228 70
Stage 1 37 75 70
Stage 2 80 153 0
Completed 0 0 0
Not Completed 117 228 70
Reason Not Completed
Death             90             187             61
Lost to Follow-up             3             2             1
Withdrawal by Subject             14             11             5
Study Terminated by Sponsor             10             28             3
Arm/Group Title Standard Taxane Therapy Trastuzumab Emtansine 2.4 mg Trastuzumab Emtansine 3.6 mg Total
Hide Arm/Group Description Docetaxel was administered at 75 mg/m^2 IV on Day 1 of a 21-day cycle, or paclitaxel was administered at 80 mg/m^2 IV weekly (Days 1, 8, and 15 of a 21 day cycle) as per investigator's choice, until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue. Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue. Trastuzumab emtansine was administered on Days 1 of a 21-day cycle at 3.6 mg/kg IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue. Total of all reporting groups
Overall Number of Baseline Participants 117 228 70 415
Hide Baseline Analysis Population Description
Intent to treat (ITT) analysis population included all randomized participants; participants grouped according to the therapy they were randomized to receive.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 117 participants 228 participants 70 participants 415 participants
62.1  (10.3) 60.5  (10.9) 61.2  (11.4) 61.1  (10.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 117 participants 228 participants 70 participants 415 participants
Female
22
  18.8%
51
  22.4%
17
  24.3%
90
  21.7%
Male
95
  81.2%
177
  77.6%
53
  75.7%
325
  78.3%
1.Primary Outcome
Title Overall Survival (OS)- Phase 3
Hide Description Overall survival was defined as the time between the date of randomization and date of death due to any cause. Kaplan-Meier estimates were used for analysis. Participants for whom no death was reported prior to an analysis cutoff (30 June 2015) was censored at the latest date before the cutoff in which they were known to be alive. All data from the standard taxane therapy and trastuzumab emtansine 2.4 mg (selected treatment arm) from phase 2 and phase 3 (Stage 2) are combined into phase 3 data, and thus cumulative data are provided within the results presented for phase 3. The confirmatory analyses are restricted to comparisons between the taxane arm and the selected trastuzumab emtansine arm (2.4 mg).
Time Frame Date of randomization until death (up to 2 years 3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants; participants grouped according to the therapy they were randomized to receive.
Arm/Group Title Standard Taxane Therapy Trastuzumab Emtansine 2.4 mg
Hide Arm/Group Description:
Docetaxel was administered at 75 mg/m^2 IV on Day 1 of a 21-day cycle, or paclitaxel was administered at 80 mg/m^2 IV weekly (Days 1, 8, and 15 of a 21 day cycle) as per investigator's choice, until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Overall Number of Participants Analyzed 117 228
Median (95% Confidence Interval)
Unit of Measure: months
8.6
(7.1 to 11.2)
7.9
(6.7 to 9.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Standard Taxane Therapy, Trastuzumab Emtansine 2.4 mg
Comments The unstratified Cox proportional hazards model was used to estimate the hazard ratio. The 95% Confidence Interval (CI) for median was computed using the method of Brookmeyer and Crowley. Reference group: Standard Taxane Therapy.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8589
Comments One sided p-value with correction for interim treatment selection due to adaptive seamless phase design.
Method Log Rank
Comments Log-Rank test, inverse normal combination test.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
0.87 to 1.60
Estimation Comments [Not Specified]
2.Primary Outcome
Title Overall Survival (OS) - Phase 2 (Dose Selection Portion of the Study)
Hide Description Overall survival was defined as the time between the date of randomization and date of death due to any cause. Kaplan-Meier estimates were used for analysis. Participants for whom no death was reported prior to an analysis cutoff (10 August 2013) was censored at the latest date before the cutoff in which they were known to be alive.
Time Frame Date of randomization until death (up to 1 year)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants that had been enrolled in phase 2 (stage 1) up to a clinical cut-off date of 10 August 2013; participants grouped according to the therapy they were randomized to receive. Here, N (number of participants analyzed)=number of evaluable participants during phase 2 up to 10 August 2013.
Arm/Group Title Standard Taxane Therapy Trastuzumab Emtansine 3.6 mg Trastuzumab Emtansine 2.4 mg
Hide Arm/Group Description:
Docetaxel was administered at 75 mg/m^2 IV on Day 1 of a 21-day cycle, or paclitaxel was administered at 80 mg/m^2 IV weekly (Days 1, 8, and 15 of a 21 day cycle) as per investigator's choice, until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab emtansine was administered on Days 1 of a 21-day cycle at 3.6 mg/kg IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Overall Number of Participants Analyzed 30 58 64
Median (95% Confidence Interval)
Unit of Measure: weeks
28.0 [1] 
(24.0 to NA)
23.0 [1] 
(18.0 to NA)
36.3 [1] 
(23.0 to NA)
[1]
The upper limit of the 95% CI could not be calculated due to the large number of censored events.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Standard Taxane Therapy, Trastuzumab Emtansine 2.4 mg
Comments The unstratified Cox proportional hazards model was used to estimate the hazard ratio. The 95% CI for median was computed using the method of Brookmeyer and Crowley. Reference group: Standard Taxane Therapy.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.32 to 2.03
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Standard Taxane Therapy, Trastuzumab Emtansine 3.6 mg
Comments The unstratified Cox proportional hazards model was used to estimate the hazard ratio. The 95% CI for median was computed using the method of Brookmeyer and Crowley. Reference group: Standard Taxane Therapy.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.01
Confidence Interval (2-Sided) 95%
0.82 to 4.92
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine 3.6 mg, Trastuzumab Emtansine 2.4 mg
Comments The unstratified Cox proportional hazards model was used to estimate the hazard ratio. The 95% CI for median was computed using the method of Brookmeyer and Crowley. Reference group: Trastuzumab Emtansine 3.6 mg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.23 to 0.96
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Disease Progression or Death According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST v1.1) - Phase 3
Hide Description Progressive disease could base on symptom deterioration or was defined as at least a 20 percent (%) increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Tumor assessment was performed using modified RECIST v1.1. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure.
Time Frame Date of randomization until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks up to 2 years 3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants; participants grouped according to the therapy they were randomized to receive.
Arm/Group Title Standard Taxane Therapy Trastuzumab Emtansine 2.4 mg
Hide Arm/Group Description:
Docetaxel was administered at 75 mg/m^2 IV on Day 1 of a 21-day cycle, or paclitaxel was administered at 80 mg/m^2 IV weekly (Days 1, 8, and 15 of a 21 day cycle) as per investigator's choice, until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Overall Number of Participants Analyzed 117 228
Measure Type: Number
Unit of Measure: percentage participants
88.9 93.0
4.Secondary Outcome
Title Progression Free Survival (PFS) According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST v1.1) - Phase 3
Hide Description Progression-free survival was defined as the time between the date of randomization and the first date of documented progression or date of death due to any cause, whichever occurred first. Tumor assessment was performed using modified RECIST v1.1. Progressive disease could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions. Kaplan-Meier estimates were used for analysis. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure. The confirmatory analyses are restricted to comparisons between the taxane arm and the selected trastuzumab emtansine arm (2.4 mg).
Time Frame Date of randomization until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks up to 2 years 3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants; participants grouped according to the therapy they were randomized to receive.
Arm/Group Title Standard Taxane Therapy Trastuzumab Emtansine 2.4 mg
Hide Arm/Group Description:
Docetaxel was administered at 75 mg/m^2 IV on Day 1 of a 21-day cycle, or paclitaxel was administered at 80 mg/m^2 IV weekly (Days 1, 8, and 15 of a 21 day cycle) as per investigator's choice, until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Overall Number of Participants Analyzed 117 228
Median (95% Confidence Interval)
Unit of Measure: months
2.89
(2.76 to 4.01)
2.66
(1.61 to 2.79)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Standard Taxane Therapy, Trastuzumab Emtansine 2.4 mg
Comments The unstratified Cox proportional hazards model was used to estimate the hazard ratio. The 95% CI for median was computed using the method of Brookmeyer and Crowley. Reference group: Standard Taxane Therapy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.308
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.89 to 1.43
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With Objective Response According to mRECIST v1.1 - Phase 3
Hide Description Objective response referred to participants with complete response (CR) or partial response (PR). CR: disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR: greater than or equal to (>=) 30% decrease in sum of the longest diameter (LD) of all target lesions taking as reference the screening sum LD. To be assigned a status of PR or CR, changes in tumor measurements had to be confirmed by repeat assessments that should have been performed no less than 4 weeks after the criteria for response were first met. Longer intervals as determined by the study protocol were also appropriate. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure.
Time Frame Date of randomization until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks up to 2 years 3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants, participants grouped according to the therapy they were randomized to receive. Here, N=number of participants with measurable disease were included in analysis of this outcome measure.
Arm/Group Title Standard Taxane Therapy Trastuzumab Emtansine 2.4 mg
Hide Arm/Group Description:
Docetaxel was administered at 75 mg/m^2 IV on Day 1 of a 21-day cycle, or paclitaxel was administered at 80 mg/m^2 IV weekly (Days 1, 8, and 15 of a 21 day cycle) as per investigator's choice, until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Overall Number of Participants Analyzed 102 204
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
19.6
(12.56 to 28.07)
20.6
(15.26 to 26.45)
6.Secondary Outcome
Title Duration of Objective Response (DOR) - Phase 3
Hide Description DOR: time from the date when a clinical response [CR or PR] was first documented to the date of first documented progressive disease (PD) or death. CR:disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR: >= 30% decrease in sum of the LD of all target lesions taking as reference the screening sum LD. PD: could base on symptom deterioration or at least a 20% increase in the sum of diameters of target or non-target lesions and new lesions, taking as reference the smallest sum on study (nadir), including baseline. To be assigned a status of PR or CR, changes in tumor measurements had to be confirmed by repeat assessments that should have been performed no less than 4 weeks after the criteria for response were first met. Longer intervals as determined by the study protocol were also appropriate. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure.
Time Frame Date of randomization until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks up to 2 years 3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants, participants grouped according to the therapy they were randomized to receive. Here, N=number of participants evaluable for this outcome measure.
Arm/Group Title Standard Taxane Therapy Trastuzumab Emtansine 2.4 mg
Hide Arm/Group Description:
Docetaxel was administered at 75 mg/m^2 IV on Day 1 of a 21-day cycle, or paclitaxel was administered at 80 mg/m^2 IV weekly (Days 1, 8, and 15 of a 21 day cycle) as per investigator's choice, until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Overall Number of Participants Analyzed 102 204
Median (95% Confidence Interval)
Unit of Measure: months
3.65
(2.76 to 5.55)
4.27
(3.02 to 6.83)
7.Secondary Outcome
Title Percentage of Participants With Clinically Significant Improvement in European Organisation for Research and Treatment of Cancer Quality of Life Core Module 30 (EORTC QLQ-C30) Score - Phase 3
Hide Description The EORTC QLQ-C30 is a validated, cancer-specific 30-item patient-reported measure, and contains 14 domains to assess the impact of cancer treatment on 5 aspects of participants functioning (physical, role, cognitive, emotional, and social), 9 aspects of disease/treatment-related symptoms (fatigue, nausea and vomiting, pain, dyspnea, insomnia, loss of appetite, constipation, diarrhea) and a global QoL/overall health status scale. Questions used 4 point scale (1 ‘Not at all’ to 4 ‘Very much’; with the exception of the QoL/health status scale which uses a 7-point scale (1 ‘very poor’ to 7 ‘Excellent’). Each scale is transformed on a scale of 0-100; a higher score equals (=) a better level of functioning or greater degree of symptoms. Change of greater than or equal to (>=) 10-points has been found to be clinically significant. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure.
Time Frame Day 1 of each treatment cycle, at the study drug completion visit, and thereafter at follow-up (up to 2 years 3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants, participants grouped according to the therapy they were randomized to receive. Here, N=number of participants with baseline and at least one post-baseline valid score.
Arm/Group Title Standard Taxane Therapy Trastuzumab Emtansine 2.4 mg
Hide Arm/Group Description:
Docetaxel was administered at 75 mg/m^2 IV on Day 1 of a 21-day cycle, or paclitaxel was administered at 80 mg/m^2 IV weekly (Days 1, 8, and 15 of a 21 day cycle) as per investigator's choice, until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Overall Number of Participants Analyzed 91 189
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Global Health Status/QoL
44.0
(33.56 to 54.75)
34.4
(27.65 to 41.36)
Appetite loss
39.6
(29.57 to 50.00)
30.2
(23.97 to 37.23)
Cognitive Functioning
31.9
(22.49 to 42.00)
28.0
(21.76 to 34.68)
Constipation
40.7
(30.48 to 51.47)
25.9
(19.84 to 32.66)
Diarrhoea
23.1
(14.89 to 32.53)
21.7
(16.23 to 28.15)
Dyspnea
19.8
(12.16 to 29.19)
21.7
(16.23 to 28.15)
Emotional Functioning
24.2
(15.98 to 33.56)
29.1
(22.74 to 35.78)
Fatigue
46.2
(36.17 to 56.92)
40.7
(33.67 to 47.81)
Nausea/Vomiting
33.0
(24.04 to 43.08)
28.0
(21.76 to 34.68)
Pain
49.5
(38.80 to 60.14)
33.9
(27.36 to 40.84)
Physical Functioning
17.6
(10.40 to 26.44)
25.9
(19.84 to 32.66)
Role Functioning
29.7
(20.55 to 39.86)
30.7
(24.20 to 37.75)
Social Functioning
34.1
(24.45 to 44.16)
37.6
(30.80 to 44.48)
Insomnia
33.0
(24.04 to 43.08)
33.3
(26.83 to 40.32)
8.Secondary Outcome
Title Percentage of Participants With Clinically Significant Improvement in Quality of Life Questionnaire Stomach Cancer Module 22 (QLQ-STO22) Score - Phase 3
Hide Description The Quality of Life Questionnaire Stomach Cancer Module 22 (QLQ-STO22) supplements the EORTC QLQ-C30 to assess symptoms and treatment-related side effects commonly reported in participants. There are 22 questions which comprise 5 scales (dysphagia, pain, reflux symptom, dietary restrictions, and anxiety) and 4 single items (dry mouth, hair loss, taste, body image). Most questions use 4-point scale (1 ‘Not at all’ to 4 ‘Very much’; 1 question was a yes or no answer). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100; higher score=better level of functioning or greater degree of symptoms. Change of >=10 points has been found to be clinically significant. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure.
Time Frame Day 1 of each treatment cycle, at the study drug completion visit, and thereafter at survival follow-up (up to 2 years 3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants, participants grouped according to the therapy they were randomized to receive. Here, N=number of participants with baseline and at least one post-baseline valid score.
Arm/Group Title Standard Taxane Therapy Trastuzumab Emtansine 2.4 mg
Hide Arm/Group Description:
Docetaxel was administered at 75 mg/m^2 IV on Day 1 of a 21-day cycle, or paclitaxel was administered at 80 mg/m^2 IV weekly (Days 1, 8, and 15 of a 21 day cycle) as per investigator's choice, until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Overall Number of Participants Analyzed 90 185
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Overall
88.9
(81.15 to 94.54)
88.1
(82.64 to 92.40)
Body image
20.0
(12.31 to 29.33)
29.7
(23.25 to 36.52)
Dry Mouth
30.0
(20.79 to 40.35)
21.1
(15.44 to 27.28)
Dietary Restrictions
41.1
(30.84 to 51.98)
32.4
(25.75 to 39.66)
Dysphagia
35.6
(25.74 to 45.80)
23.8
(17.84 to 30.31)
Hair Loss
11.1
(5.46 to 18.85)
22.7
(17.07 to 29.29)
Pain/discomfort
52.2
(41.43 to 62.45)
45.4
(38.28 to 52.87)
Specific Emotional Problems
63.3
(53.09 to 73.25)
57.8
(50.71 to 65.05)
Upper Gastrointestinal Symptoms
46.7
(36.52 to 57.49)
42.7
(35.47 to 50.00)
9.Secondary Outcome
Title Percentage of Participants With Advanced Gastric Cancer (AGC) Symptom Progression - Phase 3
Hide Description AGC symptomatic progression: a worsening of >=10-points in any 1 of the abdominal discomfort, loss of appetite, weakness and fatigue, upper abdominal pain, change in bowel movement, and/or weight loss scales of the EORTC QLQ-C30 and QLQ-STO22. QLQ-STO22 supplements EORTC QLQ-C30 to assess symptoms and commonly reported treatment-related side effects. There are 22 questions comprise 5 scales (dysphagia, pain, reflux symptom, diet restrictions, anxiety), 4 single items (dry mouth, hair loss, taste, body image), which are related to the symptoms of the disease. Most questions used 4-point scale (1 ‘Not at all’ to 4 ‘Very much’). All scores and single-items transformed to a scale of 0-100; higher score=better level of functioning or greater degree of symptoms. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure.
Time Frame Day 1 of each treatment cycle, at the study drug completion visit, and thereafter at survival follow-up (up to 2 years 3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants, participants grouped according to the therapy they were randomized to receive. Here, N=number of participants evaluable for this measure.
Arm/Group Title Standard Taxane Therapy Trastuzumab Emtansine 2.4 mg
Hide Arm/Group Description:
Docetaxel was administered at 75 mg/m^2 IV on Day 1 of a 21-day cycle, or paclitaxel was administered at 80 mg/m^2 IV weekly (Days 1, 8, and 15 of a 21 day cycle) as per investigator's choice, until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Overall Number of Participants Analyzed 117 228
Measure Type: Number
Unit of Measure: percentage of participants
90.6 93.0
10.Secondary Outcome
Title Time to Advanced Gastric Cancer (AGC) Symptom Progression - Phase 3
Hide Description Time to AGC symptom were defined as the time from randomization to the first documentation of an increase in at least one of the pre-specified abdominal discomfort, loss of appetite, weakness and fatigue, upper abdominal pain, change in bowel movement, and weight loss subscales of the QLQ STO22 and EORTC QLQ-C30. Cumulative data (up to primary analysis cut-off date of 30-June-2015) are provided for both phase 2 and phase 3 within the results of this measure.
Time Frame Day 1 of each treatment cycle, at the study drug completion visit, and thereafter at survival follow-up (up to 2 years 3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants, participants grouped according to the therapy they were randomized to receive. Here, N=number of participants evaluable for this measure.
Arm/Group Title Standard Taxane Therapy Trastuzumab Emtansine 2.4 mg
Hide Arm/Group Description:
Docetaxel was administered at 75 mg/m^2 IV on Day 1 of a 21-day cycle, or paclitaxel was administered at 80 mg/m^2 IV weekly (Days 1, 8, and 15 of a 21 day cycle) as per investigator's choice, until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Overall Number of Participants Analyzed 117 228
Median (95% Confidence Interval)
Unit of Measure: months
1.61
(1.41 to 2.17)
1.51
(1.41 to 1.64)
11.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Trastuzumab Emtansine (T-DM1) and Total Trastuzumab - Stage 1
Hide Description Maximum observed plasma concentration of Trastuzumab Emtansine (T-DM1) and total trastuzumab were reported. Stage 1 consists of all participants recruited before the regimen selection, which was carried out after 12 weeks of randomization.
Time Frame Day 1 (D1) of Cycle 1 (C1) and C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had at least one PK parameter estimated were included for analysis. Here, n=number of participants evaluable at specified timepoint.
Arm/Group Title Trastuzumab Emtansine 2.4 mg Trastuzumab Emtansine 3.6 mg
Hide Arm/Group Description:
Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab emtansine was administered on Days 1 of a 21-day cycle at 3.6 mg/kg IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Overall Number of Participants Analyzed 41 37
Mean (Standard Deviation)
Unit of Measure: microgram per milliliter (mcg/mL)
T-DM1 Cycle 1 First Dose (n=41, 37) 43.0  (11.8) 58.6  (12.9)
T-DM1 Cycle 4 First Dose (n=25, 10) 52.6  (19.4) 61.6  (14.5)
Total trastuzumab Cycle 1 First Dose (n=41, 37) 46.8  (12.3) 61.2  (14.6)
Total trastuzumab Cycle 4 First Dose (n=25, 10) 71.2  (23.2) 66.3  (14.7)
12.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) - Stage 1
Hide Description Maximum observed plasma concentration of DM1 were reported. Stage 1 consists of all participants recruited before the regimen selection decision. Regimen selection analysis was carried out after 12 weeks of randomization.
Time Frame C1D1 and C1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had at least one PK parameter estimated were included for analysis. Here, n=number of participants evaluable at specified timepoint.
Arm/Group Title Trastuzumab Emtansine 2.4 mg Trastuzumab Emtansine 3.6 mg
Hide Arm/Group Description:
Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab emtansine was administered on Days 1 of a 21-day cycle at 3.6 mg/kg IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Overall Number of Participants Analyzed 40 35
Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter (mcg/mL)
DM1 Cycle 1 First Dose (n=40, 35) 2.47  (1.05) 4.61  (6.26)
DM1 Cycle 4 First Dose (n=22, 9) 3.41  (1.61) 3.86  (0.83)
13.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Trastuzumab Emtansine (T-DM1) and Total Trastuzumab - Stage 2
Hide Description Stage 2 consists of all participants recruited after the regimen selection decision up to primary data cut-off date 30-June-2015.
Time Frame C1D1; C4D1
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had at least one PK parameter estimated were included for analysis. Here, n=number of participants evaluable at specified timepoint.
Arm/Group Title Trastuzumab Emtansine 2.4 mg
Hide Arm/Group Description:
Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Overall Number of Participants Analyzed 57
Mean (Standard Deviation)
Unit of Measure: mcg/mL
T-DM1 Cycle 1 First Dose (n=56) 34.1  (15.2)
T-DM1 Cycle 4 First Dose (n=26) 38.0  (13.4)
Total trastuzumab Cycle 1 First Dose (n=57) 44.5  (15.4)
Total trastuzumab Cycle 4 First Dose (n=26) 69.7  (21.3)
14.Secondary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf] - Stage 1
Hide Description AUCinf= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf). Stage 1 consists of all participants recruited before the regimen selection decision. Regimen selection analysis was carried out after 12 weeks of randomization.
Time Frame D1C1 and D1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had at least one PK parameter estimated were included for analysis.
Arm/Group Title Trastuzumab Emtansine 2.4 mg Trastuzumab Emtansine 3.6 mg
Hide Arm/Group Description:
Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab emtansine was administered on Days 1 of a 21-day cycle at 3.6 mg/kg IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Overall Number of Participants Analyzed 41 37
Mean (Standard Deviation)
Unit of Measure: day*mcg/mL
T-DM1 179  (51.0) 262  (90.3)
Total trastuzumab 289  (129) 403  (237)
15.Secondary Outcome
Title Plasma Decay Half-Life (t1/2) - Stage 1
Hide Description Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Stage 1 consists of all participants recruited before the regimen selection decision. Regimen selection analysis was carried out after 12 weeks of randomization.
Time Frame D1C1 and D1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had at least one PK parameter estimated were included for analysis.
Arm/Group Title Trastuzumab Emtansine 2.4 mg Trastuzumab Emtansine 3.6 mg
Hide Arm/Group Description:
Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab emtansine was administered on Days 1 of a 21-day cycle at 3.6 mg/kg IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Overall Number of Participants Analyzed 41 37
Mean (Standard Deviation)
Unit of Measure: days
T-DM1 3.48  (0.747) 3.33  (1.21)
Total trastuzumab 5.22  (1.53) 5.40  (2.15)
16.Secondary Outcome
Title Volume of Distribution at Steady State (Vss) - Stage 1
Hide Description Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. Stage 1 consists of all participants recruited before the regimen selection decision. Regimen selection analysis was carried out after 12 weeks of randomization.
Time Frame D1C1 and D1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had at least one PK parameter estimated were included for analysis.
Arm/Group Title Trastuzumab Emtansine 2.4 mg Trastuzumab Emtansine 3.6 mg
Hide Arm/Group Description:
Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab emtansine was administered on Days 1 of a 21-day cycle at 3.6 mg/kg IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Overall Number of Participants Analyzed 41 37
Mean (Standard Deviation)
Unit of Measure: milliliter per kilogram (mL/kg)
T-DM1 66.2  (19.2) 67.7  (14.0)
Total trastuzumab 65.9  (21.9) 72.1  (16.1)
17.Secondary Outcome
Title Systemic Clearance (CL) - Stage 1
Hide Description CL is a quantitative measure of the rate at which a drug substance is removed from the body. Stage 1 consists of all participants recruited before the regimen selection decision. Regimen selection analysis was carried out after 12 weeks of randomization.
Time Frame D1C1 and D1C4, C1D2, C1D3, C1D4/C1D5, C1D8, C1D15, C2D1 (up to 12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had at least one PK parameter estimated were included for analysis.
Arm/Group Title Trastuzumab Emtansine 2.4 mg Trastuzumab Emtansine 3.6 mg
Hide Arm/Group Description:
Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Trastuzumab emtansine was administered on Days 1 of a 21-day cycle at 3.6 mg/kg IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
Overall Number of Participants Analyzed 41 37
Mean (Standard Deviation)
Unit of Measure: mL/day/kg
T-DM1 14.6  (4.64) 15.4  (5.61)
Total trastuzumab 10.2  (4.87) 11.3  (5.46)
Time Frame Baseline up to data cut-off date 30-April-2016 (up to 3 years 8 months)
Adverse Event Reporting Description Safety Analysis Population included all participants who received at least one dose of study medication. The safety parameters were analyzed and presented according to the therapy participants received. Cumulative data (up to primary analysis cut-off date of 30-April-2016) are provided for both phase 2 and phase 3.
 
Arm/Group Title Standard Taxane Therapy Trastuzumab Emtansine 2.4 mg Trastuzumab Emtansine 3.6 mg
Hide Arm/Group Description Docetaxel was administered at 75 mg/m^2 IV on Day 1 of a 21-day cycle, or paclitaxel was administered at 80 mg/m^2 IV weekly (Days 1, 8, and 15 of a 21 day cycle) as per investigator's choice, until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue. Trastuzumab emtansine was administered on Days 1, 8, and 15 of a 21-day cycle at 2.4 milligram per kilogram (mg/kg) IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue. Trastuzumab emtansine was administered on Days 1 of a 21-day cycle at 3.6 mg/kg IV infusion until progression of disease, intolerable toxicity, initiation of another anticancer therapy, or participants and/or physician decision to discontinue.
All-Cause Mortality
Standard Taxane Therapy Trastuzumab Emtansine 2.4 mg Trastuzumab Emtansine 3.6 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Standard Taxane Therapy Trastuzumab Emtansine 2.4 mg Trastuzumab Emtansine 3.6 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   31/111 (27.93%)   65/224 (29.02%)   23/69 (33.33%) 
Blood and lymphatic system disorders       
Anaemia * 1  3/111 (2.70%)  8/224 (3.57%)  2/69 (2.90%) 
Coagulopathy * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Disseminated intravascular coagulation * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Febrile neutropenia * 1  4/111 (3.60%)  1/224 (0.45%)  0/69 (0.00%) 
Neutropenia * 1  3/111 (2.70%)  0/224 (0.00%)  0/69 (0.00%) 
Thrombocytopenia * 1  0/111 (0.00%)  3/224 (1.34%)  0/69 (0.00%) 
Cardiac disorders       
Atrial fibrillation * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Cardiac failure * 1  0/111 (0.00%)  0/224 (0.00%)  1/69 (1.45%) 
Supraventricular tachycardia * 1  1/111 (0.90%)  0/224 (0.00%)  0/69 (0.00%) 
Gastrointestinal disorders       
Abdominal pain * 1  1/111 (0.90%)  0/224 (0.00%)  1/69 (1.45%) 
Diarrhoea * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Dysphagia * 1  1/111 (0.90%)  2/224 (0.89%)  1/69 (1.45%) 
Gastric haemorrhage * 1  2/111 (1.80%)  6/224 (2.68%)  4/69 (5.80%) 
Gastric ulcer haemorrhage * 1  0/111 (0.00%)  0/224 (0.00%)  1/69 (1.45%) 
Gastrointestinal haemorrhage * 1  1/111 (0.90%)  5/224 (2.23%)  0/69 (0.00%) 
Gastrointestinal ulcer * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Haematemesis * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Ileus * 1  0/111 (0.00%)  2/224 (0.89%)  1/69 (1.45%) 
Intestinal obstruction * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Jejunal perforation * 1  1/111 (0.90%)  0/224 (0.00%)  0/69 (0.00%) 
Lower gastrointestinal haemorrhage * 1  1/111 (0.90%)  0/224 (0.00%)  0/69 (0.00%) 
Nausea * 1  0/111 (0.00%)  0/224 (0.00%)  1/69 (1.45%) 
Oesophageal haemorrhage * 1  0/111 (0.00%)  3/224 (1.34%)  0/69 (0.00%) 
Oesophageal stenosis * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Pancreatitis * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Regurgitation * 1  1/111 (0.90%)  0/224 (0.00%)  0/69 (0.00%) 
Small intestinal haemorrhage * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Upper gastrointestinal haemorrhage * 1  0/111 (0.00%)  8/224 (3.57%)  1/69 (1.45%) 
Vomiting * 1  1/111 (0.90%)  1/224 (0.45%)  1/69 (1.45%) 
General disorders       
Death * 1  1/111 (0.90%)  0/224 (0.00%)  0/69 (0.00%) 
Fatigue * 1  2/111 (1.80%)  0/224 (0.00%)  0/69 (0.00%) 
General physical health deterioration * 1  0/111 (0.00%)  0/224 (0.00%)  1/69 (1.45%) 
Pyrexia * 1  1/111 (0.90%)  2/224 (0.89%)  3/69 (4.35%) 
Hepatobiliary disorders       
Bile duct stenosis * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Cholangitis acute * 1  0/111 (0.00%)  0/224 (0.00%)  1/69 (1.45%) 
Immune system disorders       
Anaphylactic reaction * 1  2/111 (1.80%)  0/224 (0.00%)  0/69 (0.00%) 
Hypersensitivity * 1  1/111 (0.90%)  0/224 (0.00%)  0/69 (0.00%) 
Infections and infestations       
Atypical pneumonia * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Cellulitis * 1  0/111 (0.00%)  0/224 (0.00%)  1/69 (1.45%) 
Device related infection * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Escherichia infection * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Gastrointestinal infection * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Infection * 1  0/111 (0.00%)  2/224 (0.89%)  0/69 (0.00%) 
Lower respiratory tract infection * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Lung abscess * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Lung infection * 1  0/111 (0.00%)  0/224 (0.00%)  1/69 (1.45%) 
Meningitis * 1  0/111 (0.00%)  0/224 (0.00%)  1/69 (1.45%) 
Pneumonia * 1  5/111 (4.50%)  7/224 (3.13%)  2/69 (2.90%) 
Respiratory tract infection * 1  1/111 (0.90%)  1/224 (0.45%)  0/69 (0.00%) 
Sepsis * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Septic shock * 1  0/111 (0.00%)  2/224 (0.89%)  0/69 (0.00%) 
Staphylococcal sepsis * 1  1/111 (0.90%)  0/224 (0.00%)  0/69 (0.00%) 
Urinary tract infection * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Intervertebral discitis * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Injury, poisoning and procedural complications       
Facial bones fracture * 1  1/111 (0.90%)  0/224 (0.00%)  0/69 (0.00%) 
Fall * 1  0/111 (0.00%)  0/224 (0.00%)  1/69 (1.45%) 
Overdose * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Investigations       
Blood bilirubin increased * 1  0/111 (0.00%)  4/224 (1.79%)  0/69 (0.00%) 
Blood creatinine increased * 1  0/111 (0.00%)  2/224 (0.89%)  0/69 (0.00%) 
Hepatic enzyme increased * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Liver function test abnormal * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Dehydration * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Diabetes mellitus * 1  0/111 (0.00%)  0/224 (0.00%)  1/69 (1.45%) 
Hyperglycaemia * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Hypophagia * 1  0/111 (0.00%)  0/224 (0.00%)  1/69 (1.45%) 
Musculoskeletal and connective tissue disorders       
Back pain * 1  1/111 (0.90%)  0/224 (0.00%)  0/69 (0.00%) 
Myalgia * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Bladder transitional cell carcinoma * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Myelodysplastic syndrome * 1  0/111 (0.00%)  0/224 (0.00%)  1/69 (1.45%) 
Tumour haemorrhage * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Nervous system disorders       
Encephalopathy * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Hepatic encephalopathy * 1  0/111 (0.00%)  2/224 (0.89%)  0/69 (0.00%) 
Metabolic encephalopathy * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Subarachnoid haemorrhage * 1  0/111 (0.00%)  0/224 (0.00%)  1/69 (1.45%) 
Syncope * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Psychiatric disorders       
Confusional state * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Renal and urinary disorders       
Acute kidney injury * 1  0/111 (0.00%)  1/224 (0.45%)  1/69 (1.45%) 
Respiratory, thoracic and mediastinal disorders       
Interstitial lung disease * 1  1/111 (0.90%)  1/224 (0.45%)  0/69 (0.00%) 
Pleural effusion * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Pneumonia aspiration * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Pneumonitis * 1  1/111 (0.90%)  2/224 (0.89%)  0/69 (0.00%) 
Pulmonary alveolar haemorrhage * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Pulmonary embolism * 1  1/111 (0.90%)  0/224 (0.00%)  0/69 (0.00%) 
Pulmonary oedema * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
Respiratory failure * 1  1/111 (0.90%)  0/224 (0.00%)  0/69 (0.00%) 
Aspiration * 1  0/111 (0.00%)  1/224 (0.45%)  0/69 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Standard Taxane Therapy Trastuzumab Emtansine 2.4 mg Trastuzumab Emtansine 3.6 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   105/111 (94.59%)   211/224 (94.20%)   62/69 (89.86%) 
Blood and lymphatic system disorders       
Anaemia * 1  35/111 (31.53%)  75/224 (33.48%)  15/69 (21.74%) 
Febrile neutropenia * 1  7/111 (6.31%)  1/224 (0.45%)  0/69 (0.00%) 
Leukopenia * 1  10/111 (9.01%)  2/224 (0.89%)  1/69 (1.45%) 
Neutropenia * 1  55/111 (49.55%)  24/224 (10.71%)  7/69 (10.14%) 
Thrombocytopenia * 1  3/111 (2.70%)  60/224 (26.79%)  18/69 (26.09%) 
Gastrointestinal disorders       
Abdominal distension * 1  4/111 (3.60%)  10/224 (4.46%)  6/69 (8.70%) 
Abdominal pain * 1  12/111 (10.81%)  42/224 (18.75%)  10/69 (14.49%) 
Abdominal pain upper * 1  8/111 (7.21%)  19/224 (8.48%)  6/69 (8.70%) 
Constipation * 1  22/111 (19.82%)  47/224 (20.98%)  10/69 (14.49%) 
Diarrhoea * 1  27/111 (24.32%)  33/224 (14.73%)  10/69 (14.49%) 
Dry mouth * 1  2/111 (1.80%)  20/224 (8.93%)  4/69 (5.80%) 
Dyspepsia * 1  11/111 (9.91%)  17/224 (7.59%)  6/69 (8.70%) 
Dysphagia * 1  4/111 (3.60%)  9/224 (4.02%)  4/69 (5.80%) 
Nausea * 1  30/111 (27.03%)  57/224 (25.45%)  15/69 (21.74%) 
Stomatitis * 1  21/111 (18.92%)  14/224 (6.25%)  3/69 (4.35%) 
Vomiting * 1  15/111 (13.51%)  41/224 (18.30%)  17/69 (24.64%) 
General disorders       
Asthenia * 1  9/111 (8.11%)  39/224 (17.41%)  9/69 (13.04%) 
Chills * 1  2/111 (1.80%)  12/224 (5.36%)  4/69 (5.80%) 
Fatigue * 1  51/111 (45.95%)  68/224 (30.36%)  24/69 (34.78%) 
Malaise * 1  5/111 (4.50%)  12/224 (5.36%)  1/69 (1.45%) 
Mucosal inflammation * 1  7/111 (6.31%)  8/224 (3.57%)  1/69 (1.45%) 
Oedema peripheral * 1  16/111 (14.41%)  14/224 (6.25%)  5/69 (7.25%) 
Pain * 1  11/111 (9.91%)  6/224 (2.68%)  3/69 (4.35%) 
Pyrexia * 1  17/111 (15.32%)  44/224 (19.64%)  11/69 (15.94%) 
Investigations       
Alanine aminotransferase increased * 1  4/111 (3.60%)  21/224 (9.38%)  5/69 (7.25%) 
Aspartate aminotransferase increased * 1  5/111 (4.50%)  36/224 (16.07%)  10/69 (14.49%) 
Blood alkaline phosphatase increased * 1  3/111 (2.70%)  8/224 (3.57%)  5/69 (7.25%) 
Blood bilirubin increased * 1  3/111 (2.70%)  13/224 (5.80%)  1/69 (1.45%) 
Weight decereased * 1  8/111 (7.21%)  13/224 (5.80%)  3/69 (4.35%) 
Metabolism and nutrition disorders       
Deceased appetite * 1  32/111 (28.83%)  57/224 (25.45%)  22/69 (31.88%) 
Hypoalbuminaemia * 1  5/111 (4.50%)  13/224 (5.80%)  3/69 (4.35%) 
Hypokalaemia * 1  1/111 (0.90%)  22/224 (9.82%)  3/69 (4.35%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  13/111 (11.71%)  13/224 (5.80%)  6/69 (8.70%) 
Back pain * 1  6/111 (5.41%)  13/224 (5.80%)  6/69 (8.70%) 
Myalgia * 1  18/111 (16.22%)  13/224 (5.80%)  6/69 (8.70%) 
Nervous system disorders       
Dizziness * 1  5/111 (4.50%)  14/224 (6.25%)  5/69 (7.25%) 
Dysgeusia * 1  11/111 (9.91%)  18/224 (8.04%)  5/69 (7.25%) 
Headache * 1  6/111 (5.41%)  24/224 (10.71%)  2/69 (2.90%) 
Neuropathy peripheral * 1  11/111 (9.91%)  22/224 (9.82%)  2/69 (2.90%) 
Peripheral sensory neuropathy * 1  22/111 (19.82%)  21/224 (9.38%)  4/69 (5.80%) 
Psychiatric disorders       
Depression * 1  0/111 (0.00%)  5/224 (2.23%)  4/69 (5.80%) 
Insominia * 1  10/111 (9.01%)  18/224 (8.04%)  5/69 (7.25%) 
Respiratory, thoracic and mediastinal disorders       
Cough * 1  12/111 (10.81%)  13/224 (5.80%)  7/69 (10.14%) 
Dyspnoea * 1  9/111 (8.11%)  21/224 (9.38%)  10/69 (14.49%) 
Hiccups * 1  8/111 (7.21%)  5/224 (2.23%)  6/69 (8.70%) 
Epistaxis * 1  6/111 (5.41%)  26/224 (11.61%)  7/69 (10.14%) 
Skin and subcutaneous tissue disorders       
Alopecia * 1  57/111 (51.35%)  7/224 (3.13%)  1/69 (1.45%) 
Nail disorder * 1  7/111 (6.31%)  4/224 (1.79%)  0/69 (0.00%) 
Palmar−plantar erythrodysaesthesia syndrome * 1  8/111 (7.21%)  8/224 (3.57%)  2/69 (2.90%) 
Pruritus * 1  11/111 (9.91%)  7/224 (3.13%)  4/69 (5.80%) 
Rash * 1  12/111 (10.81%)  15/224 (6.70%)  3/69 (4.35%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.0
The study was terminated by the Sponsor as the primary analysis results did not meet the primary endpoint.
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-LaRoche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01641939     History of Changes
Other Study ID Numbers: BO27952
2012-000660-22 ( EudraCT Number )
First Submitted: July 13, 2012
First Posted: July 17, 2012
Results First Submitted: June 30, 2016
Results First Posted: August 11, 2016
Last Update Posted: May 12, 2017