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A Study of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy in Patients With HER2-Positive Breast Cancer Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Preoperative Therapy (KATHERINE)

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ClinicalTrials.gov Identifier: NCT01772472
Recruitment Status : Active, not recruiting
First Posted : January 21, 2013
Results First Posted : October 1, 2019
Last Update Posted : June 28, 2021
Sponsor:
Collaborators:
NSABP Foundation Inc
German Breast Group
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
Drug: trastuzumab emtansine
Enrollment 1486
Recruitment Details  
Pre-assignment Details 1486 patients were randomized in 268 centers across 28 countries.
Arm/Group Title Trastuzumab Trastuzumab Emtansine
Hide Arm/Group Description Participants received trastuzumab 6 milligrams/kilogram (mg/kg) intravenously (IV) every 3 weeks for 14 cycles. Participants received trastuzumab emtansine 3.6 mg/kg IV every 3 weeks for 14 cycles.
Period Title: Overall Study
Started 743 743
Completed 0 0
Not Completed 743 743
Reason Not Completed
Death             56             42
Physician Decision             1             3
Other             5             5
Lost to Follow-up             12             8
Withdrawal by Subject             72             50
Ongoing             597             635
Arm/Group Title Trastuzumab Trastuzumab Emtansine Total
Hide Arm/Group Description Participants received trastuzumab 6 milligrams/kilogram (mg/kg) intravenously (IV) every 3 weeks for 14 cycles. Participants received trastuzumab emtansine 3.6 mg/kg IV every 3 weeks for 14 cycles. Total of all reporting groups
Overall Number of Baseline Participants 743 743 1486
Hide Baseline Analysis Population Description
The intent-to-treat (ITT) population was defined as all participants enrolled in the study regardless of whether or not they received any study drug.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 743 participants 743 participants 1486 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
675
  90.8%
685
  92.2%
1360
  91.5%
>=65 years
68
   9.2%
58
   7.8%
126
   8.5%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 743 participants 743 participants 1486 participants
Female
740
  99.6%
741
  99.7%
1481
  99.7%
Male
3
   0.4%
2
   0.3%
5
   0.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 743 participants 743 participants 1486 participants
American Indian or Alaska Native
50
   6.7%
36
   4.8%
86
   5.8%
Asian
64
   8.6%
65
   8.7%
129
   8.7%
Native Hawaiian or Other Pacific Islander
1
   0.1%
0
   0.0%
1
   0.1%
Black or African American
19
   2.6%
21
   2.8%
40
   2.7%
White
531
  71.5%
551
  74.2%
1082
  72.8%
More than one race
1
   0.1%
1
   0.1%
2
   0.1%
Unknown or Not Reported
77
  10.4%
69
   9.3%
146
   9.8%
1.Primary Outcome
Title Invasive Disease-free Survival (IDFS)
Hide Description IDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer. 3-year IDFS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after randomization.
Time Frame From randomization to data cut-off date of 25 July 2018 (approximately up to 64 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population comprised all randomized patients, whether or not they received any study treatment or completed a full course of study treatment. Patients were analyzed according to their randomized treatment.
Arm/Group Title Trastuzumab Trastuzumab Emtansine
Hide Arm/Group Description:
Participants received trastuzumab 6 milligrams/kilogram (mg/kg) intravenously (IV) every 3 weeks for 14 cycles.
Participants received trastuzumab emtansine 3.6 mg/kg IV every 3 weeks for 14 cycles.
Overall Number of Participants Analyzed 743 743
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent Probability
77.02
(73.78 to 80.26)
88.27
(85.81 to 90.72)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trastuzumab, Trastuzumab Emtansine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.50
Confidence Interval 95%
0.39 to 0.64
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Invasive Disease-free Survival Including Second Primary Non-breast Cancer
Hide Description IDFS including second primary non-breast cancer was defined the same way as IDFS for the primary endpoint but including second primary non breast invasive cancer as an event (with the exception of non-melanoma skin cancers and carcinoma in situ (CIS) of any site). 3-year IDFS including second primary non-breast cancer event-free rates per treatment arm in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after randomization.
Time Frame From baseline up to 10 years
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Disease-free Survival
Hide Description Disease-free survival was defined as the time between randomization and the date of the first occurrence of an invasive disease-free survival event including second primary non-breast cancer event or contralateral or ipsilateral DCIS. 3-year DFS event-free rates per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after randomization.
Time Frame From baseline up to 10 years
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival in the overall study population was defined as the time from the date of randomization to the date of death from any cause. 5 years OS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 5 years after treatment.
Time Frame Baseline up to 10 years
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Distant Recurrence-Free Interval (DRFI)
Hide Description DRFI was defined as the time between randomization and the date of distant breast cancer recurrence. 3 years DRFI event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after treatment.
Time Frame Baseline up to 10 years
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Percentage of Participants With Adverse Events
Hide Description An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs, including AEs of Special Interest and AEs of Particular Interest, were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs).
Time Frame From Day 1 to 30 days after last dose of study drug, up to the clinical cutoff date (approximately 64 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population was defined as all participants who have received at least one dose of study medication.
Arm/Group Title Trastuzumab Trastuzumab Emtansine
Hide Arm/Group Description:
Participants received trastuzumab 6 milligrams/kilogram (mg/kg) intravenously (IV) every 3 weeks for 14 cycles.
Participants received trastuzumab emtansine 3.6 mg/kg IV every 3 weeks for 14 cycles.
Overall Number of Participants Analyzed 720 740
Measure Type: Number
Unit of Measure: Percentage of Participants
93.3 98.8
7.Secondary Outcome
Title Percentage of Participants With Cardiac Dysfunction
Hide Description Cardiac events were reported based on the NCI-CTCAE, v4.0.
Time Frame From baseline up to 10 years
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Change From Baseline of Functional Scales, Symptom Scales and Single Items in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30)
Hide Description The EORTC QLQ-C30 included global health status, functional scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea/vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to 0 - 100 scale, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 - 10 points considered to be a minimally important difference to participants. A positive value means an increase, while a negative value means a decrease, in score at the indicated time-point relative to the score at baseline (Cycle 1, Day 1).
Time Frame Baseline, Cycle 5, 11, Follow-up (FU) Month 6, Follow-up Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized Patient Population of patients with both a baseline assessment and at least one post-baseline assessment are included in the analysis.
Arm/Group Title Trastuzumab Trastuzumab Emtansine
Hide Arm/Group Description:
Participants received trastuzumab 6 milligrams/kilogram (mg/kg) intravenously (IV) every 3 weeks for 14 cycles.
Participants received trastuzumab emtansine 3.6 mg/kg IV every 3 weeks for 14 cycles.
Overall Number of Participants Analyzed 743 743
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Baseline: Appetite Loss Number Analyzed 624 participants 645 participants
7.9  (17.4) 7.1  (16.4)
Change at Cycle 5: Appetite Loss Number Analyzed 558 participants 571 participants
1.0  (18.7) 6.5  (23.7)
Change at Cycle 11: Appetite Loss Number Analyzed 496 participants 496 participants
-0.5  (17.2) 2.9  (20.2)
Change at FU Month 6: Appetite Loss Number Analyzed 410 participants 462 participants
-1.6  (18.3) -1.7  (19.9)
Change at FU Month 12: Appetite Loss Number Analyzed 384 participants 430 participants
0.5  (20.3) -1.9  (20.1)
Baseline: Constipation Number Analyzed 624 participants 645 participants
9.8  (20.2) 9.5  (19.0)
Change at Cycle 5: Constipation Number Analyzed 558 participants 571 participants
1.0  (22.4) 4.6  (22.6)
Change at Cycle 11: Constipation Number Analyzed 496 participants 496 participants
3.4  (23.6) 7.3  (23.1)
Change at FU Month 6: Constipation Number Analyzed 410 participants 462 participants
4.1  (23.7) 3.7  (23.3)
Change at FU Month 12: Constipation Number Analyzed 384 participants 430 participants
3.2  (23.2) 4.3  (24.6)
Baseline: Diarrhea Number Analyzed 624 participants 645 participants
8.8  (17.6) 6.4  (14.9)
Change at Cycle 5: Diarrhea Number Analyzed 558 participants 571 participants
-1.6  (19.3) -1.5  (19.5)
Change at Cycle 11: Diarrhea Number Analyzed 496 participants 496 participants
-0.4  (21.4) -2.4  (17.5)
Change at FU Month 6: Diarrhea Number Analyzed 410 participants 462 participants
-3.4  (18.5) -1.9  (18.3)
Change at FU Month 12: Diarrhea Number Analyzed 384 participants 430 participants
-2.8  (18.9) -1.6  (18.4)
Baseline: Dyspnea Number Analyzed 624 participants 645 participants
12.7  (20.7) 11.0  (18.8)
Change at Cycle 5: Dyspnea Number Analyzed 558 participants 571 participants
2.3  (21.9) 4.1  (22.4)
Change at Cycle 11: Dyspnea Number Analyzed 496 participants 496 participants
2.8  (21.2) 2.7  (20.4)
Change at FU Month 6: Dyspnea Number Analyzed 410 participants 462 participants
3.3  (22.8) 3.8  (22.7)
Change at FU Month 12: Dyspnea Number Analyzed 384 participants 430 participants
3.9  (24.9) 5.3  (22.4)
Baseline: Fatigue Number Analyzed 624 participants 645 participants
29.2  (21.1) 28.0  (20.0)
Change at Cycle 5: Fatigue Number Analyzed 558 participants 571 participants
1.1  (20.1) 5.5  (19.7)
Change at Cycle 11: Fatigue Number Analyzed 496 participants 496 participants
1.1  (20.5) 3.8  (21.3)
Change at FU Month 6: Fatigue Number Analyzed 410 participants 462 participants
-1.4  (21.9) -0.1  (22.2)
Change at FU Month 12: Fatigue Number Analyzed 384 participants 430 participants
-0.1  (23.3) -0.1  (22.1)
Baseline: Financial Difficulties Number Analyzed 604 participants 635 participants
28.6  (33.3) 27.6  (31.9)
Change at Cycle 5: Financial Difficulties Number Analyzed 530 participants 548 participants
-3.1  (26.5) -3.0  (28.0)
Change at Cycle 11: Financial Difficulties Number Analyzed 472 participants 480 participants
-5.1  (27.6) -1.7  (28.7)
Change at FU Month 6: Financial Difficulties Number Analyzed 393 participants 444 participants
-8.4  (28.3) -6.5  (30.6)
Change at FU Month 12: Financial Difficulties Number Analyzed 367 participants 413 participants
-10.9  (30.5) -7.3  (31.0)
Baseline: Insomnia Number Analyzed 624 participants 645 participants
30.6  (30.8) 30.6  (29.2)
Change at Cycle 5: Insomnia Number Analyzed 558 participants 571 participants
1.9  (28.4) 1.3  (29.7)
Change at Cycle 11: Insomnia Number Analyzed 494 participants 494 participants
2.4  (29.9) 1.5  (30.3)
Change at FU Month 6: Insomnia Number Analyzed 410 participants 462 participants
1.8  (31.3) -0.9  (32.1)
Change at FU Month 12: Insomnia Number Analyzed 384 participants 430 participants
0.3  (30.4) 0.7  (31.7)
Baseline: Nausea/Vomiting Number Analyzed 624 participants 645 participants
3.3  (9.0) 2.8  (8.0)
Change at Cycle 5: Nausea/Vomiting Number Analyzed 558 participants 571 participants
1.5  (11.2) 3.2  (12.5)
Change at Cycle 11: Nausea/Vomiting Number Analyzed 496 participants 496 participants
1.3  (12.8) 3.0  (11.8)
Change at FU Month 6: Nausea/Vomiting Number Analyzed 410 participants 462 participants
0.8  (10.4) 0.2  (11.1)
Change at FU Month 12: Nausea/Vomiting Number Analyzed 384 participants 430 participants
0.4  (10.5) 1.2  (10.9)
Baseline: Pain Number Analyzed 624 participants 645 participants
22.2  (22.2) 22.6  (22.8)
Change at Cycle 5: Pain Number Analyzed 558 participants 571 participants
0.0  (23.2) 1.8  (23.9)
Change at Cycle 11: Pain Number Analyzed 496 participants 496 participants
0.1  (23.1) 2.1  (24.4)
Change at FU Month 6: Pain Number Analyzed 410 participants 462 participants
-0.3  (24.6) -0.5  (24.3)
Change at FU Month 12: Pain Number Analyzed 384 participants 430 participants
-1.2  (25.6) -0.8  (25.4)
Baseline: Cognitive Functioning Number Analyzed 624 participants 645 participants
83.3  (20.2) 84.4  (19.0)
Change at Cycle 5: Cognitive Functioning Number Analyzed 558 participants 571 participants
-3.8  (18.4) -4.5  (18.7)
Change at Cycle 11: Cognitive Functioning Number Analyzed 496 participants 496 participants
-5.4  (21.3) -5.3  (19.6)
Change at FU Month 6: Cognitive Functioning Number Analyzed 410 participants 462 participants
-4.1  (22.0) -6.1  (21.6)
Change at FU Month 12: Cognitive Functioning Number Analyzed 384 participants 430 participants
-4.9  (22.2) -6.9  (21.7)
Baseline: Emotional Functioning Number Analyzed 624 participants 645 participants
75.0  (22.0) 75.2  (21.2)
Change at Cycle 5: Emotional Functioning Number Analyzed 558 participants 571 participants
-0.4  (20.0) -1.3  (21.3)
Change at Cycle 11: Emotional Functioning Number Analyzed 496 participants 496 participants
-1.0  (21.3) 0.1  (22.0)
Change at FU Month 6: Emotional Functioning Number Analyzed 410 participants 462 participants
-2.9  (22.0) -0.8  (23.3)
Change at FU Month 12: Emotional Functioning Number Analyzed 384 participants 430 participants
-2.0  (22.7) -1.6  (23.5)
Baseline: Physical Functioning Number Analyzed 624 participants 645 participants
84.5  (15.3) 85.8  (14.1)
Change at Cycle 5: Physical Functioning Number Analyzed 558 participants 571 participants
0.3  (12.9) -1.6  (12.7)
Change at Cycle 11: Physical Functioning Number Analyzed 496 participants 496 participants
1.9  (14.2) -0.6  (14.6)
Change at FU Month 6: Physical Functioning Number Analyzed 410 participants 462 participants
2.8  (15.4) 0.7  (15.1)
Change at FU Month 12: Physical Functioning Number Analyzed 384 participants 430 participants
2.7  (14.5) 0.8  (14.5)
Baseline: Role Functioning Number Analyzed 624 participants 645 participants
77.5  (25.0) 78.6  (23.3)
Change at Cycle 5: Role Functioning Number Analyzed 558 participants 571 participants
2.0  (24.3) -0.2  (24.1)
Change at Cycle 11: Role Functioning Number Analyzed 496 participants 496 participants
4.0  (24.3) 0.6  (24.5)
Change at FU Month 6: Role Functioning Number Analyzed 410 participants 462 participants
7.4  (25.8) 3.6  (26.7)
Change at FU Month 12: Role Functioning Number Analyzed 384 participants 430 participants
8.0  (27.5) 4.6  (25.5)
Baseline: Social Functioning Number Analyzed 624 participants 645 participants
77.1  (24.1) 76.8  (23.2)
Change at Cycle 5: Social Functioning Number Analyzed 558 participants 571 participants
4.0  (22.5) 1.6  (23.8)
Change at Cycle 11: Social Functioning Number Analyzed 496 participants 496 participants
5.8  (24.0) 2.5  (23.6)
Change at FU Month 6: Social Functioning Number Analyzed 410 participants 462 participants
8.5  (23.7) 6.5  (26.1)
Change at FU Month 12: Social Functioning Number Analyzed 384 participants 430 participants
9.5  (25.1) 7.4  (26.4)
Baseline: Global Health Status Number Analyzed 624 participants 645 participants
71.2  (19.3) 71.4  (18.0)
Change at Cycle 5: Global Health Status Number Analyzed 558 participants 571 participants
0.6  (18.9) -1.9  (19.6)
Change at Cycle 11: Global Health Status Number Analyzed 496 participants 496 participants
1.7  (17.8) -0.5  (19.9)
Change at FU Month 6: Global Health Status Number Analyzed 410 participants 462 participants
2.5  (19.3) 2.0  (19.2)
Change at FU Month 12: Global Health Status Number Analyzed 384 participants 430 participants
3.2  (19.5) 2.8  (20.1)
9.Secondary Outcome
Title Change From Baseline of Four Functioning Scales and Four Symptom Scales in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Breast Cancer (QLQ-BR23)
Hide Description EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores averaged and transformed to 0-100 scale. High score for functional scale indicated high/better level of functioning/healthy functioning. Higher scores for symptom scales represent higher levels of symptoms/problems. For functional scales, positive change from baseline indicated deterioration in quality of life (QOL) and negative change from baseline indicated an improvement in QOL. For symptom scales, positive change from baseline indicated an improvement in quality of life (QOL) and negative change from baseline indicated a deterioration in QOL.
Time Frame Baseline, Cycle 5, 11, Follow-up Month 6, Follow-up Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized Patient Population of patients with both a baseline assessment and at least one post-baseline assessment are included in the analysis.
Arm/Group Title Trastuzumab Trastuzumab Emtansine
Hide Arm/Group Description:
Participants received trastuzumab 6 milligrams/kilogram (mg/kg) intravenously (IV) every 3 weeks for 14 cycles.
Participants received trastuzumab emtansine 3.6 mg/kg IV every 3 weeks for 14 cycles.
Overall Number of Participants Analyzed 743 743
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Baseline: Body Image Number Analyzed 622 participants 645 participants
69.8  (28.5) 67.5  (28.5)
Change at Cycle 5: Body Image Number Analyzed 555 participants 571 participants
1.5  (20.5) 4.6  (22.7)
Change at Cycle 11: Body Image Number Analyzed 493 participants 495 participants
3.4  (24.4) 5.7  (23.9)
Change at FU Month 6: Body Image Number Analyzed 409 participants 462 participants
3.6  (25.1) 7.8  (25.8)
Change at FU Month 12: Body Image Number Analyzed 383 participants 428 participants
6.2  (27.1) 6.1  (27.2)
Baseline: FP Number Analyzed 622 participants 645 participants
51.3  (31.2) 50.1  (31.7)
Change at Cycle 5: FP Number Analyzed 555 participants 571 participants
2.6  (28.3) 6.5  (29.9)
Change at Cycle 11: FP Number Analyzed 493 participants 495 participants
6.3  (30.0) 6.1  (31.4)
Change at FU Month 6: FP Number Analyzed 409 participants 462 participants
7.7  (33.5) 8.1  (34.6)
Change at FU Month 12: FP Number Analyzed 383 participants 428 participants
8.1  (31.1) 8.2  (33.0)
Baseline: Sexual Enjoyment Number Analyzed 218 participants 241 participants
50.9  (28.8) 52.3  (28.5)
Change at Cycle 5: Sexual Enjoyment Number Analyzed 147 participants 172 participants
2.3  (26.4) -1.9  (24.6)
Change at Cycle 11: Sexual Enjoyment Number Analyzed 128 participants 137 participants
4.4  (27.5) 4.4  (24.5)
Change at FU Month 6: Sexual Enjoyment Number Analyzed 104 participants 126 participants
3.2  (28.1) 0.3  (27.5)
Change at FU Month 12: Sexual Enjoyment Number Analyzed 95 participants 114 participants
5.6  (26.0) 1.8  (26.2)
Baseline: Sexual Function Number Analyzed 550 participants 564 participants
20.2  (23.6) 22.0  (23.4)
Change at Cycle 5: Sexual Function Number Analyzed 456 participants 466 participants
3.3  (20.0) 2.3  (20.0)
Change at Cycle 11: Sexual Function Number Analyzed 393 participants 382 participants
3.1  (20.8) 1.9  (20.3)
Change at FU Month 6: Sexual Function Number Analyzed 321 participants 360 participants
5.1  (23.9) 4.3  (23.1)
Change at FU Month 12: Sexual Function Number Analyzed 289 participants 319 participants
5.9  (23.7) 5.2  (22.7)
Baseline: Arm Symptoms Number Analyzed 622 participants 645 participants
24.6  (21.1) 24.5  (21.0)
Change at Cycle 5: Arm Symptoms Number Analyzed 555 participants 571 participants
-2.8  (20.9) -2.6  (23.0)
Change at Cycle 11: Arm Symptoms Number Analyzed 493 participants 495 participants
-2.6  (21.2) 0.2  (24.2)
Change at FU Month 6: Arm Symptoms Number Analyzed 409 participants 462 participants
-3.0  (23.5) -1.3  (24.2)
Change at FU Month 12: Arm Symptoms Number Analyzed 383 participants 428 participants
-5.7  (22.8) -1.5  (22.6)
Baseline: Breast Symptoms Number Analyzed 622 participants 645 participants
22.7  (19.1) 21.4  (17.9)
Change at Cycle 5: Breast Symptoms Number Analyzed 555 participants 571 participants
-1.1  (20.3) -1.1  (19.1)
Change at Cycle 11: Breast Symptoms Number Analyzed 493 participants 495 participants
-3.7  (19.8) -0.6  (19.5)
Change at FU Month 6: Breast Function Number Analyzed 409 participants 462 participants
-6.5  (20.0) -2.2  (19.7)
Change at Follow-up Month 12: Breast Function Number Analyzed 383 participants 428 participants
-8.3  (19.9) -3.8  (19.2)
Baseline: Systemic Therapy Side Effects (SE) Number Analyzed 622 participants 645 participants
16.7  (13.7) 16.9  (14.1)
Change at Cycle 5: Systemic Therapy SE Number Analyzed 555 participants 571 participants
0.7  (13.0) 5.5  (15.3)
Change at Cycle 11: Systemic Therapy SE Number Analyzed 493 participants 495 participants
1.2  (12.2) 4.2  (15.4)
Change at FU Month 6: Systemic Therapy SE Number Analyzed 409 participants 462 participants
1.9  (13.9) 1.1  (15.3)
Change at FU Month 12: Systemic Therapy SE Number Analyzed 383 participants 428 participants
1.3  (13.9) 1.4  (16.3)
Baseline: Upset by Hair Loss Item Number Analyzed 77 participants 96 participants
40.3  (35.6) 50.7  (38.4)
Change at Cycle 5: Upset by Hair Loss Item Number Analyzed 13 participants 17 participants
-5.1  (38.1) -17.6  (39.3)
Change at Cycle 11: Upset by Hair Loss Item Number Analyzed 14 participants 14 participants
-28.6  (45.0) -14.3  (33.9)
Change at FU Month 6: Upset by Hair Loss Item Number Analyzed 25 participants 22 participants
-12.0  (47.0) -15.2  (42.1)
Change at FU Month 12: Upset by Hair Loss Item Number Analyzed 23 participants 21 participants
-2.9  (37.5) -14.3  (41.6)
10.Secondary Outcome
Title Serum Concentrations (Area Under the Concentration-time Curve [AUC]) of Trastuzumab Emtansine (Including Total Trastuzumab and DM1)
Hide Description Blood and serum samples for measurement of trastuzumab emtansine, total trastuzumab, and DM1 will be obtained from patients randomized to the trastuzumab emtansine arm.
Time Frame Cycle (C) 1, Day (D) 1 and C4D1 of pre-infusion, C1D1 and C4D1 post-infusion, C2D1 and C5D1 pre-infusion and study treatment termination
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Serum Concentrations (AUC) of Trastuzumab
Hide Description Serum blood samples were collected for trastuzumab measurement prior to dosing and 15-30 minutes post infusion for Cycle 1 and Cycle 4. Additional serum samples were collected at study treatment termination.
Time Frame C1D1 and C4D1 of post-infusion and study treatment termination
Outcome Measure Data Not Reported
Time Frame From baseline to primary clinical cutoff date of approximately 64 months
Adverse Event Reporting Description Safety population was analyzed.
 
Arm/Group Title Trastuzumab Trastuzumab Emtansine
Hide Arm/Group Description Participants received trastuzumab 6 milligrams/kilogram (mg/kg) intravenously (IV) every 3 weeks for 14 cycles. Participants received trastuzumab emtansine 3.6 mg/kg IV every 3 weeks for 14 cycles.
All-Cause Mortality
Trastuzumab Trastuzumab Emtansine
Affected / at Risk (%) Affected / at Risk (%)
Total   56/720 (7.78%)      42/740 (5.68%)    
Hide Serious Adverse Events
Trastuzumab Trastuzumab Emtansine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   58/720 (8.06%)      94/740 (12.70%)    
Cardiac disorders     
Cardiac Failure  1  2/720 (0.28%)  2 2/740 (0.27%)  2
Atrial Fibrillation  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Pericarditis  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Eye disorders     
Vision Blurred  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Gastrointestinal disorders     
Vomiting  1  2/720 (0.28%)  3 3/740 (0.41%)  4
Abdominal Pain  1  1/720 (0.14%)  2 3/740 (0.41%)  3
Diarrhoea  1  1/720 (0.14%)  1 1/740 (0.14%)  1
Nausea  1  1/720 (0.14%)  2 1/740 (0.14%)  1
Colitis  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Haemorrhoids  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Ileal Perforation  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Impaired gastric Emptying  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Large Intestinal Obstruction  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Pancreatitis  1  1/720 (0.14%)  1 0/740 (0.00%)  0
General disorders     
Non-Cardiac Chest pain  1  2/720 (0.28%)  2 3/740 (0.41%)  3
Influenza Like Illness  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Pyrexia  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Systemic Inflammatory Response Syndrome  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis  1  1/720 (0.14%)  1 1/740 (0.14%)  1
Nodular Regenerative Hyperplasia  1  0/720 (0.00%)  0 2/740 (0.27%)  2
Gallbladder Polyp  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Hepatic Cyst  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Hepatitis  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Immune system disorders     
Hypersensitivity  1  0/720 (0.00%)  0 4/740 (0.54%)  4
Infections and infestations     
Mastitis  1  6/720 (0.83%)  7 8/740 (1.08%)  8
Device Related Infection  1  0/720 (0.00%)  0 6/740 (0.81%)  6
Bronchitis  1  1/720 (0.14%)  1 3/740 (0.41%)  3
Pneumonia  1  1/720 (0.14%)  1 3/740 (0.41%)  3
Skin Infection  1  2/720 (0.28%)  2 2/740 (0.27%)  2
Lung Infection  1  1/720 (0.14%)  1 2/740 (0.27%)  2
Urinary Tract Infection  1  2/720 (0.28%)  2 1/740 (0.14%)  1
Wound Infection  1  2/720 (0.28%)  2 1/740 (0.14%)  1
Appendicitis  1  0/720 (0.00%)  0 2/740 (0.27%)  2
Cellulitis  1  1/720 (0.14%)  1 1/740 (0.14%)  1
Gastroenteritis  1  0/720 (0.00%)  0 2/740 (0.27%)  2
Abscess Intestinal  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Cystitis  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Diverticulitis  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Enterocolitis Infections  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Implant Site Cellulitis  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Infected Seroma  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Influenza  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Perirectal Abscess  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Staphylococcal Bacteraemia  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Tonsillitis  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Vestibular Neuronitis  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Vulvitis  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Injury, poisoning and procedural complications     
Wound Dehiscence  1  1/720 (0.14%)  1 3/740 (0.41%)  3
Post Procedural haemorrhage  1  1/720 (0.14%)  1 1/740 (0.14%)  1
Radiation Pneumonitis  1  0/720 (0.00%)  0 2/740 (0.27%)  2
Tibia Fracture  1  0/720 (0.00%)  0 2/740 (0.27%)  2
Ankle Fracture  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Femur Fracture  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Limb Fracture  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Seroma  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Wound Complication  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Wrist Fracture  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Investigations     
Platelet Count Decreased  1  0/720 (0.00%)  0 10/740 (1.35%)  10
Aspartate Aminotransferase Increased  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Ejection Fraction Decreased  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Troponin T Increased  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Metabolism and nutrition disorders     
Hyperglycaemia  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back Pain  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Muscular Weakness  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Colon Cancer Stage 1  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Endometrial Adenocarcinoma  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Intraductal Proliferative Breast Lesion  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Pituitary Tumour Benign  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Nervous system disorders     
Peripheral Sensory Neuropathy  1  0/720 (0.00%)  0 3/740 (0.41%)  3
Peripheral Motor Neuropathy  1  0/720 (0.00%)  0 2/740 (0.27%)  2
Syncope  1  0/720 (0.00%)  0 2/740 (0.27%)  2
Dizziness  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Haemorrhage intracranial  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Neuralgia  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Paraesthesia  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Psychiatric disorders     
Anxiety  1  0/720 (0.00%)  0 1/740 (0.14%)  2
Suicidal Ideation  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Renal and urinary disorders     
Acute Kidney Injury  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Bladder Pain  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Reproductive system and breast disorders     
Ovarian Cyst  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Menorrhagia  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Uterine Haemorrhage  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Uterine Obstruction  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Uterine Prolapse  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Epistaxis  1  0/720 (0.00%)  0 2/740 (0.27%)  2
Pneumonitis  1  0/720 (0.00%)  0 2/740 (0.27%)  2
Aspiration  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Chronic Obstructive Pulmonary  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Dyspnoea  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Pleural Effusion  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Pulmonary fibrosis  1  0/720 (0.00%)  0 1/740 (0.14%)  1
Skin and subcutaneous tissue disorders     
Photosensitivity reaction  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Telangiectasia  1  1/720 (0.14%)  1 0/740 (0.00%)  0
Vascular disorders     
Embolism  1  3/720 (0.42%)  3 1/740 (0.14%)  1
Hypertension  1  1/720 (0.14%)  1 1/740 (0.14%)  1
Haematoma  1  1/720 (0.14%)  1 0/740 (0.00%)  0
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Trastuzumab Trastuzumab Emtansine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   634/720 (88.06%)      719/740 (97.16%)    
Blood and lymphatic system disorders     
Anaemia  1  60/720 (8.33%)  79 74/740 (10.00%)  89
Eye disorders     
lacrimation Increased  1  13/720 (1.81%)  13 41/740 (5.54%)  44
Gastrointestinal disorders     
Nausea  1  93/720 (12.92%)  111 308/740 (41.62%)  438
Constipation  1  59/720 (8.19%)  66 126/740 (17.03%)  152
Diarrhoea  1  89/720 (12.36%)  116 91/740 (12.30%)  117
Vomiting  1  37/720 (5.14%)  45 106/740 (14.32%)  139
Dry Mouth  1  9/720 (1.25%)  9 100/740 (13.51%)  109
Stomatitis  1  27/720 (3.75%)  29 80/740 (10.81%)  96
Abdominal Pain  1  42/720 (5.83%)  48 55/740 (7.43%)  66
General disorders     
Fatigue  1  243/720 (33.75%)  276 366/740 (49.46%)  456
Influenza like Illness  1  86/720 (11.94%)  96 100/740 (13.51%)  138
Pain  1  92/720 (12.78%)  113 93/740 (12.57%)  114
Pyrexia  1  29/720 (4.03%)  32 76/740 (10.27%)  98
Oedema Peripheral  1  52/720 (7.22%)  56 29/740 (3.92%)  33
Chills  1  14/720 (1.94%)  16 39/740 (5.27%)  57
Infections and infestations     
Upper Respiratory Tract Infection  1  53/720 (7.36%)  65 58/740 (7.84%)  69
Urinary Tract Infection  1  37/720 (5.14%)  39 64/740 (8.65%)  79
Injury, poisoning and procedural complications     
Radiation Skin Injury  1  199/720 (27.64%)  208 188/740 (25.41%)  198
Investigations     
Aspartate Aminotransferase Increased  1  40/720 (5.56%)  44 209/740 (28.24%)  253
Platelet Count Decreased  1  17/720 (2.36%)  21 205/740 (27.70%)  256
Alanine Aminotransferase Increased  1  41/720 (5.69%)  51 171/740 (23.11%)  208
White Blood Cell Count Decreased  1  42/720 (5.83%)  62 61/740 (8.24%)  81
Neutrophil Count Decreased  1  36/720 (5.00%)  46 61/740 (8.24%)  78
Blood Alkaline Phosphatase Increased  1  13/720 (1.81%)  14 61/740 (8.24%)  68
Blood Bilirubin Increased  1  2/720 (0.28%)  2 49/740 (6.62%)  74
Metabolism and nutrition disorders     
Decreased Appetite  1  16/720 (2.22%)  19 62/740 (8.38%)  70
Hypokalaemia  1  14/720 (1.94%)  20 48/740 (6.49%)  58
Musculoskeletal and connective tissue disorders     
Arthralgia  1  148/720 (20.56%)  162 192/740 (25.95%)  221
Myalgia  1  80/720 (11.11%)  87 114/740 (15.41%)  125
Pain In Extremity  1  70/720 (9.72%)  81 86/740 (11.62%)  97
Back Pain  1  66/720 (9.17%)  73 53/740 (7.16%)  56
Bone Pain  1  35/720 (4.86%)  38 52/740 (7.03%)  55
Muscle Spasms  1  45/720 (6.25%)  45 33/740 (4.46%)  36
Nervous system disorders     
Headache  1  122/720 (16.94%)  146 210/740 (28.38%)  287
Peripheral Sensory Neuropathy  1  50/720 (6.94%)  51 135/740 (18.24%)  146
Dizziness  1  57/720 (7.92%)  61 69/740 (9.32%)  76
Paraesthesia  1  40/720 (5.56%)  43 60/740 (8.11%)  72
Dysgeusia  1  11/720 (1.53%)  12 60/740 (8.11%)  61
Psychiatric disorders     
Insomnia  1  86/720 (11.94%)  95 101/740 (13.65%)  110
Depression  1  44/720 (6.11%)  47 41/740 (5.54%)  44
Anxiety  1  42/720 (5.83%)  44 27/740 (3.65%)  29
Reproductive system and breast disorders     
Breast pain  1  42/720 (5.83%)  50 53/740 (7.16%)  56
Respiratory, thoracic and mediastinal disorders     
Cough  1  86/720 (11.94%)  93 100/740 (13.51%)  112
Epistaxis  1  25/720 (3.47%)  30 158/740 (21.35%)  220
Dyspnoea  1  52/720 (7.22%)  56 62/740 (8.38%)  69
Oropharyngeal Pain  1  33/720 (4.58%)  36 37/740 (5.00%)  39
Skin and subcutaneous tissue disorders     
Pruritus  1  42/720 (5.83%)  44 51/740 (6.89%)  57
Dry Skin  1  36/720 (5.00%)  41 48/740 (6.49%)  52
Rash Maculo-Papular  1  26/720 (3.61%)  27 42/740 (5.68%)  49
Dermatitis Acneiform  1  21/720 (2.92%)  23 39/740 (5.27%)  44
Vascular disorders     
Hot Flush  1  146/720 (20.28%)  154 95/740 (12.84%)  99
Lymphoedema  1  48/720 (6.67%)  51 37/740 (5.00%)  37
Hypertension  1  34/720 (4.72%)  38 41/740 (5.54%)  58
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
EMail: genentech@druginfo.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01772472    
Other Study ID Numbers: BO27938
2012-002018-37 ( EudraCT Number )
First Submitted: January 17, 2013
First Posted: January 21, 2013
Results First Submitted: July 24, 2019
Results First Posted: October 1, 2019
Last Update Posted: June 28, 2021