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Trial record 62 of 173 for:    pertuzumab

A Study Evaluating Trastuzumab Emtansine Plus Pertuzumab Compared With Chemotherapy Plus Trastuzumab and Pertuzumab for Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer

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ClinicalTrials.gov Identifier: NCT02131064
Recruitment Status : Completed
First Posted : May 6, 2014
Results First Posted : June 8, 2017
Last Update Posted : July 2, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Breast Neoplasms
Interventions Drug: Carboplatin
Drug: Docetaxel
Drug: Pertuzumab
Drug: Trastuzumab
Drug: Trastuzumab Emtansine
Enrollment 444
Recruitment Details  
Pre-assignment Details A total of 574 participants were screened at 65 sites in 10 countries, of which 444 participants were randomized in two arms: Trastuzumab (TCH) + Pertuzumab (P) (Arm A) and Trastuzumab Emtansine (TDM1) + P (Arm B)
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles). Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Period Title: Overall Study
Started 221 223
Completed 196 189
Not Completed 25 34
Reason Not Completed
Death             5             6
Lost to Follow-up             4             8
Withdrawal by Subject             14             18
Other             2             2
Arm/Group Title TCH + P T-DM1 + P Total
Hide Arm/Group Description Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles). Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period). Total of all reporting groups
Overall Number of Baseline Participants 221 223 444
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 221 participants 223 participants 444 participants
49.3  (11.2) 50.5  (10.6) 49.9  (10.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 221 participants 223 participants 444 participants
Female
221
 100.0%
222
  99.6%
443
  99.8%
Male
0
   0.0%
1
   0.4%
1
   0.2%
1.Primary Outcome
Title Percentage of Participants With Total Pathological Complete Response (tpCR) Assessed Based on Tumor Samples
Hide Description tpCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes ( that is [i.e.], ypT0/is, ypN0 in the American Joint Committee on Cancer [AJCC] staging system, 7th edition). Percentage of participants with tpCR was reported.
Time Frame Pre-surgery (within 6 weeks after neoadjuvant therapy; up to approximately 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (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 TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 221 223
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
56.1
(49.29 to 62.76)
44.4
(37.76 to 51.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TCH + P, T-DM1 + P
Comments 95% CI for the difference in tPCR rates between treatment arms was calculated using normal approximation.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0126
Comments Threshold for significance at 5%
Method Cochran-Mantel-Haenszel Chi-Square
Comments The Cochran-Mantel-Haenszel Chi-square test was used and stratified by local hormone receptor status and clinical stage at presentation.
Method of Estimation Estimation Parameter Difference in tpCR rate
Estimated Value -11.71
Confidence Interval (2-Sided) 95%
-20.95 to -2.48
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival
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. 3 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 3 years after treatment.
Time Frame From randomization until death (up to approximately 47 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 TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 221 223
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Probability
97.6
(95.5 to 99.7)
97.0
(94.6 to 99.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TCH + P, T-DM1 + P
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7557
Comments [Not Specified]
Method Cochran-Mantel-Haenszel Chi-Square Test
Comments The Cochran-Mantel-Haenszel Chi-square test was used and stratified by local hormone receptor status and clinical stage at presentation.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.21
Confidence Interval (2-Sided) 95%
0.37 to 3.96
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants Who Received Breast-Conserving Surgery (BCS)
Hide Description BCS rate was defined as the percentage of participants who achieve BCS out of the ITT population of participants without inflammatory breast cancer.
Time Frame Surgery performed after completion of neoadjuvant therapy (approximately 6 months after neoadjuvant period)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 213 218
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
52.6
(45.65 to 59.45)
41.7
(35.12 to 48.33)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TCH + P, T-DM1 + P
Comments 95% CI for the difference in BCS rate between treatment arms was calculated using normal approximation.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0228
Comments [Not Specified]
Method Cochran-Mantel-Haenszel Chi-Square
Comments The Cochran-Mantel-Haenszel Chi-square test was used and stratified by local hormone receptor status and clinical stage at presentation.
Method of Estimation Estimation Parameter Difference in BCS rate
Estimated Value -10.84
Confidence Interval (2-Sided) 95%
-20.21 to -1.47
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Event-Free Survival
Hide Description Event-free survival (EFS) is defined as the time from randomization to disease progression or disease recurrence (local, regional, distant, or contralateral, invasive or non-invasive), or death from any cause. 3 years EFS 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 From randomization up to disease progression or recurrence or death (up to approximately 47 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 TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 221 223
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Probability
94.21
(91.02 to 97.39)
85.28
(80.47 to 90.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TCH + P, T-DM1 + P
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0027
Comments [Not Specified]
Method Log Rank
Comments The Log Rank was used and stratified by local hormone receptor status and clinical stage at presentation.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.61
Confidence Interval (2-Sided) 95%
1.36 to 4.98
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Invasive Disease-free Survival (IDFS)
Hide Description IDFS is defined only for participants who undergo surgery. IDFS is defined as the time from surgery to the first documented occurrence of an IDFS event, defined as: Ipsilateral invasive breast tumor recurrence; Ipsilateral local−regional invasive breast cancer recurrence; Distant recurrence; Contralateral invasive breast cancer; and death from any cause. 3 years of 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 treatment.
Time Frame From surgery to the first documented occurrence of IDFC event (up to approximately 47 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 TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 221 223
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Probability
91.99
(86.73 to 97.26)
93.04
(89.39 to 96.69)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TCH + P, T-DM1 + P
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.52 to 2.40
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants by Response for Neuropathy Single Item
Hide Description Participants answered the question “Did you have tingling hands/feet?”, from the Modified Quality of Life Questionnaire Breast Cancer 23 (mQLQ-BR23), on a 5-point scale (1 ‘Not at all’, 2 ‘A little’, 3 'Somewhat', 4 ‘Quite a bit’, 5 ‘Very much’). Percentage of participants by each response was reported.
Time Frame Baseline,Cycle(C) 3,C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4 (approx 47 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population of patients with both a baseline assessment and at least one post-treatment assessment in the respective single question are included in the analysis.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 221 223
Measure Type: Number
Unit of Measure: Percentage of Participants
Not at all: Baseline Number Analyzed 198 participants 204 participants
78.7 81.2
A little bit: Baseline Number Analyzed 198 participants 204 participants
9.5 9.4
Somewhat: Baseline Number Analyzed 198 participants 204 participants
0 0
Quite a bit: Baseline Number Analyzed 198 participants 204 participants
0.9 0.9
Very much: Baseline Number Analyzed 198 participants 204 participants
0.5 0
Not at all: Neoadjuvant Cycle 3 Number Analyzed 177 participants 183 participants
54.3 59.6
A little bit: Neoadjuvant Cycle 3 Number Analyzed 177 participants 183 participants
20.8 19.3
Somewhat: Neoadjuvant Cycle 3 Number Analyzed 177 participants 183 participants
0 0
Quite a bit: Neoadjuvant Cycle 3 Number Analyzed 177 participants 183 participants
3.2 2.7
Very much: Neoadjuvant Cycle 3 Number Analyzed 177 participants 183 participants
1.8 0.4
Not at all: Neoadjuvant Cycle 5 Number Analyzed 182 participants 178 participants
37.1 54.3
A little bit: Neoadjuvant Cycle 5 Number Analyzed 182 participants 178 participants
29.9 21.1
Somewhat: Neoadjuvant Cycle 5 Number Analyzed 182 participants 178 participants
0 0
Quite a bit: Neoadjuvant Cycle 5 Number Analyzed 182 participants 178 participants
8.6 2.7
Very much: Neoadjuvant Cycle 5 Number Analyzed 182 participants 178 participants
6.8 1.8
Not at all: Pre-Surgery Number Analyzed 170 participants 171 participants
22.6 52.0
A little bit: Pre-Surgery Number Analyzed 170 participants 171 participants
29.0 17.9
Somewhat: Pre-Surgery Number Analyzed 170 participants 171 participants
0 0
Quite a bit: Pre-Surgery Number Analyzed 170 participants 171 participants
15.4 5.4
Very much: Pre-Surgery Number Analyzed 170 participants 171 participants
10.0 1.3
Not at all: Adjuvant Cycle 4 Number Analyzed 174 participants 155 participants
31.2 42.6
A little bit: Adjuvant Cycle 4 Number Analyzed 174 participants 155 participants
31.7 15.2
Somewhat: Adjuvant Cycle 4 Number Analyzed 174 participants 155 participants
0 0
Quite a bit: Adjuvant Cycle 4 Number Analyzed 174 participants 155 participants
9.5 9.0
Very much: Adjuvant Cycle 4 Number Analyzed 174 participants 155 participants
6.3 2.7
Not at all: Adjuvant Cycle 8 Number Analyzed 168 participants 143 participants
33.0 31.8
A little bit: Adjuvant Cycle 8 Number Analyzed 168 participants 143 participants
28.1 19.3
Somewhat: Adjuvant Cycle 8 Number Analyzed 168 participants 143 participants
0 0
Quite a bit: Adjuvant Cycle 8 Number Analyzed 168 participants 143 participants
10.9 9.0
Very much: Adjuvant Cycle 8 Number Analyzed 168 participants 143 participants
4.1 4.0
Not at all: End of Therapy Number Analyzed 172 participants 165 participants
31.2 31.4
A little bit: End of Therapy Number Analyzed 172 participants 165 participants
30.8 23.8
Somewhat: End of Therapy Number Analyzed 172 participants 165 participants
0 0
Quite a bit: End of Therapy Number Analyzed 172 participants 165 participants
10.9 12.1
Very much: End of Therapy Number Analyzed 172 participants 165 participants
5.0 6.7
Not at all: Follow-up 2 Number Analyzed 150 participants 136 participants
38.0 32.7
A little bit: Follow-up 2 Number Analyzed 150 participants 136 participants
19.9 19.3
Somewhat: Follow-up 2 Number Analyzed 150 participants 136 participants
0 0
Quite a bit: Follow-up 2 Number Analyzed 150 participants 136 participants
5.9 7.6
Very much: Follow-up 2 Number Analyzed 150 participants 136 participants
4.1 1.3
Not at all: Follow-up 4 Number Analyzed 136 participants 124 participants
39.8 32.7
A little bit: Follow-up 4 Number Analyzed 136 participants 124 participants
15.4 17.9
Somewhat: Follow-up 4 Number Analyzed 136 participants 124 participants
0 0
Quite a bit: Follow-up 4 Number Analyzed 136 participants 124 participants
4.1 3.1
Very much: Follow-up 4 Number Analyzed 136 participants 124 participants
2.3 1.8
7.Secondary Outcome
Title Percentage of Participants by Response for Skin Problem Single Items
Hide Description Participants answered the Question 1 “Did itching skin bother you?” and Question 2 “Have you had skin problems?”, from the mQLQ-BR23, on a 5-point scale (1 ‘Not at all’, 2 ‘A little’, 3 'Somewhat', 4 ‘Quite a bit’, 5 ‘Very much’). Percentage of participants by each response was reported.
Time Frame Baseline,Cycle(C) 3,C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4 (approx 47 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population of patients with both a baseline assessment and at least one post-treatment assessment in the respective single question are included in the analysis.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 221 223
Measure Type: Number
Unit of Measure: Percentage of Participants
Q1: Not at all: Baseline Number Analyzed 197 participants 204 participants
71.9 72.6
Q1: A little bit: Baseline Number Analyzed 197 participants 204 participants
14.9 16.1
Q1: Somewhat: Baseline Number Analyzed 197 participants 204 participants
0 0
Q1: Quite a bit: Baseline Number Analyzed 197 participants 204 participants
2.3 2.2
Q1: Very much: Baseline Number Analyzed 197 participants 204 participants
0 0.4
Q1: Not at all: Neoadjuvant Cycle 3 Number Analyzed 176 participants 183 participants
35.3 48.9
Q1: A little bit: Neoadjuvant Cycle 3 Number Analyzed 176 participants 183 participants
31.2 27.4
Q1: Somewhat: Neoadjuvant Cycle 3 Number Analyzed 176 participants 183 participants
0 0
Q1: Quite a bit: Neoadjuvant Cycle 3 Number Analyzed 176 participants 183 participants
10.9 4.0
Q1: Very much: Neoadjuvant Cycle 3 Number Analyzed 176 participants 183 participants
2.3 1.8
Q1: Not at all: Neoadjuvant Cycle 5 Number Analyzed 181 participants 178 participants
48.9 46.2
Q1: A little bit: Neoadjuvant Cycle 5 Number Analyzed 181 participants 178 participants
23.1 26.0
Q1: Somewhat: Neoadjuvant Cycle 5 Number Analyzed 181 participants 178 participants
0 0
Q1: Quite a bit: Neoadjuvant Cycle 5 Number Analyzed 181 participants 178 participants
7.7 6.3
Q1: Very much: Neoadjuvant Cycle 5 Number Analyzed 181 participants 178 participants
2.3 1.3
Q1: Not at all: Pre-Surgery Number Analyzed 170 participants 171 participants
40.3 48.0
Q1: A little bit: Pre-Surgery Number Analyzed 170 participants 171 participants
26.7 21.5
Q1: Somewhat: Pre-Surgery Number Analyzed 170 participants 171 participants
0 0
Q1: Quite a bit: Pre-Surgery Number Analyzed 170 participants 171 participants
7.2 5.8
Q1: Very much: Pre-Surgery Number Analyzed 170 participants 171 participants
2.7 1.3
Q1: Not at all: Adjuvant Cycle 4 Number Analyzed 173 participants 155 participants
38.5 39.0
Q1: A little bit: Adjuvant Cycle 4 Number Analyzed 173 participants 155 participants
23.5 21.5
Q1: Somewhat: Adjuvant Cycle 4 Number Analyzed 173 participants 155 participants
0 0
Q1: Quite a bit: Adjuvant Cycle 4 Number Analyzed 173 participants 155 participants
9.5 6.7
Q1: Very much: Adjuvant Cycle 4 Number Analyzed 173 participants 155 participants
6.8 2.2
Q1: Not at all: Adjuvant Cycle 8 Number Analyzed 167 participants 143 participants
34.8 39.0
Q1: A little bit: Adjuvant Cycle 8 Number Analyzed 167 participants 143 participants
27.6 15.7
Q1: Somewhat: Adjuvant Cycle 8 Number Analyzed 167 participants 143 participants
0 0
Q1: Quite a bit: Adjuvant Cycle 8 Number Analyzed 167 participants 143 participants
9.0 6.3
Q1: Very much: Adjuvant Cycle 8 Number Analyzed 167 participants 143 participants
4.1 3.1
Q1: Not at all: End of Therapy Number Analyzed 171 participants 165 participants
39.4 42.6
Q1: A little bit: End of Therapy Number Analyzed 171 participants 165 participants
26.7 22.9
Q1: Somewhat: End of Therapy Number Analyzed 171 participants 165 participants
0 0
Q1: Quite a bit: End of Therapy Number Analyzed 171 participants 165 participants
6.8 6.7
Q1: Very much: End of Therapy Number Analyzed 171 participants 165 participants
4.5 1.8
Q1: Not at all: Follow-up 2 Number Analyzed 149 participants 136 participants
43.9 39.9
Q1: A little bit: Follow-up 2 Number Analyzed 149 participants 136 participants
19.0 14.8
Q1: Somewhat: Follow-up 2 Number Analyzed 149 participants 136 participants
0 0
Q1: Quite a bit: Follow-up 2 Number Analyzed 149 participants 136 participants
3.6 4.0
Q1: Very much: Follow-up 2 Number Analyzed 149 participants 136 participants
0.9 2.2
Q1: Not at all: Follow-up 4 Number Analyzed 135 participants 124 participants
46.2 37.7
Q1: A little bit: Follow-up 4 Number Analyzed 135 participants 124 participants
10.4 12.1
Q1: Somewhat: Follow-up 4 Number Analyzed 135 participants 124 participants
0 0
Q1: Quite a bit: Follow-up 4 Number Analyzed 135 participants 124 participants
3.2 4.5
Q1: Very much: Follow-up 4 Number Analyzed 135 participants 124 participants
1.4 1.3
Q2: Not at all: Baseline Number Analyzed 198 participants 204 participants
64.7 67.3
Q2: A little bit: Baseline Number Analyzed 198 participants 204 participants
21.3 17.9
Q2: Somewhat: Baseline Number Analyzed 198 participants 204 participants
0 0
Q2: Quite a bit: Baseline Number Analyzed 198 participants 204 participants
3.2 5.8
Q2: Very much: Baseline Number Analyzed 198 participants 204 participants
0.5 0.4
Q2: Not at all: Neoadjuvant Cycle 3 Number Analyzed 177 participants 183 participants
14.0 24.2
Q2: A little bit: Neoadjuvant Cycle 3 Number Analyzed 177 participants 183 participants
40.7 38.6
Q2: Somewhat: Neoadjuvant Cycle 3 Number Analyzed 177 participants 183 participants
0 0
Q2: Quite a bit: Neoadjuvant Cycle 3 Number Analyzed 177 participants 183 participants
18.6 14.8
Q2: Very much: Neoadjuvant Cycle 3 Number Analyzed 177 participants 183 participants
6.8 4.5
Q2: Not at all: Neoadjuvant Cycle 5 Number Analyzed 182 participants 178 participants
21.3 25.6
Q2: A little bit: Neoadjuvant Cycle 5 Number Analyzed 182 participants 178 participants
35.7 37.7
Q2: Somewhat: Neoadjuvant Cycle 5 Number Analyzed 182 participants 178 participants
0 0
Q2: Quite a bit: Neoadjuvant Cycle 5 Number Analyzed 182 participants 178 participants
20.4 12.6
Q2: Very much: Neoadjuvant Cycle 5 Number Analyzed 182 participants 178 participants
5.0 4.0
Q2: Not at all: Pre-Surgery Number Analyzed 170 participants 171 participants
21.3 27.4
Q2: A little bit: Pre-Surgery Number Analyzed 170 participants 171 participants
33.9 37.2
Q2: Somewhat: Pre-Surgery Number Analyzed 170 participants 171 participants
0 0
Q2: Quite a bit: Pre-Surgery Number Analyzed 170 participants 171 participants
15.4 8.1
Q2: Very much: Pre-Surgery Number Analyzed 170 participants 171 participants
6.3 4.0
Q2: Not at all: Adjuvant Cycle 4 Number Analyzed 174 participants 155 participants
23.5 24.2
Q2: A little bit: Adjuvant Cycle 4 Number Analyzed 174 participants 155 participants
33.0 30.9
Q2: Somewhat: Adjuvant Cycle 4 Number Analyzed 174 participants 155 participants
0 0
Q2: Quite a bit: Adjuvant Cycle 4 Number Analyzed 174 participants 155 participants
13.1 9.4
Q2: Very much: Adjuvant Cycle 4 Number Analyzed 174 participants 155 participants
9.0 4.9
Q2: Not at all: Adjuvant Cycle 8 Number Analyzed 168 participants 143 participants
23.1 25.6
Q2: A little bit: Adjuvant Cycle 8 Number Analyzed 168 participants 143 participants
35.7 24.2
Q2: Somewhat: Adjuvant Cycle 8 Number Analyzed 168 participants 143 participants
0 0
Q2: Quite a bit: Adjuvant Cycle 8 Number Analyzed 168 participants 143 participants
12.2 9.9
Q2: Very much: Adjuvant Cycle 8 Number Analyzed 168 participants 143 participants
5.0 4.5
Q2: Not at all: End of Therapy Number Analyzed 172 participants 165 participants
27.1 27.4
Q2: A little bit: End of Therapy Number Analyzed 172 participants 165 participants
33.9 30.0
Q2: Somewhat: End of Therapy Number Analyzed 172 participants 165 participants
0 0
Q2: Quite a bit: End of Therapy Number Analyzed 172 participants 165 participants
10.0 13.5
Q2: Very much: End of Therapy Number Analyzed 172 participants 165 participants
6.8 3.1
Q2: Not at all: Follow-up 2 Number Analyzed 150 participants 136 participants
36.2 27.8
Q2: A little bit: Follow-up 2 Number Analyzed 150 participants 136 participants
25.8 25.6
Q2: Somewhat: Follow-up 2 Number Analyzed 150 participants 136 participants
0 0
Q2: Quite a bit: Follow-up 2 Number Analyzed 150 participants 136 participants
4.1 6.3
Q2: Very much: Follow-up 2 Number Analyzed 150 participants 136 participants
1.8 1.3
Q2: Not at all: Follow-up 4 Number Analyzed 136 participants 124 participants
39.8 30.0
Q2: A little bit: Follow-up 4 Number Analyzed 136 participants 124 participants
14.5 18.8
Q2: Somewhat: Follow-up 4 Number Analyzed 136 participants 124 participants
0 0
Q2: Quite a bit: Follow-up 4 Number Analyzed 136 participants 124 participants
4.5 4.5
Q2: Very much: Follow-up 4 Number Analyzed 136 participants 124 participants
2.7 2.2
8.Secondary Outcome
Title Percentage of Participants With a Clinically Meaningful Deterioration in Global Health Status (GHS)/Quality of Life (QoL) Score
Hide Description Participants rated their quality of life (global health status) on European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ- C30), with total scores ranging from 0 (worst) to 100 (best); where higher score indicates better quality of life. Clinically meaningful deterioration in GHS/QoL was defined as a decrease in score of 10 points in GHS/QoL.
Time Frame From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) Population comprised all randomized participants, whether or not they received any study treatment or completed a full course of study treatment. Participants were analyzed according to their randomized treatment. As per protocol, the analysis for this outcome measure was focused on the neoadjuvant period only.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 193 205
Measure Type: Number
Unit of Measure: Percentage of Participants
69.9 45.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TCH + P, T-DM1 + P
Comments 95% CI for the difference in clinically meaningful deterioration in GHS/QoL score between treatment arms was calculated using normal approximation.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Deterioration
Estimated Value -24.58
Confidence Interval (2-Sided) 95%
-33.98 to -15.19
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Time to Clinically Meaningful Deterioration in GHS/QoL Score
Hide Description Participants rated their quality of life (global health status) on EORTC QLQ C-30, with total scores ranging from 0 (worst) to 100 (best); where higher score indicates better quality of life. Time to deterioration was defined as the time from baseline to first 10-point (or greater) decrease as measured by GHS/QoL. All valid GHS/QoL questionnaires of the neoadjuvant phase including surgery were used. Participants without deterioration were censored at the time of completing the last GHS/QoL plus 1 day. Median time to deterioration was estimated with Kaplan-Meier method. The 95% confidence interval (CI) for the median was computed using the method of Brookmeyer and Crowley.
Time Frame From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) Population comprised all randomized participants, whether or not they received any study treatment or completed a full course of study treatment. Participants were analyzed according to their randomized treatment. As per protocol, the analysis for this outcome measure was focused on the neoadjuvant period only.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 191 200
Median (95% Confidence Interval)
Unit of Measure: months
3.02
(2.83 to 3.38)
4.63
(4.11 to 7.98)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TCH + P, T-DM1 + P
Comments Stratified cox proportional hazards regression model was used to estimate Hazard Ratio and CI. Stratification by hormonal receptor status and clinical stage at presentation (stratification factors).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Log Rank
Comments Log Rank was used and stratified by local hormone receptor status and clinical stage at presentation.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.46 to 0.78
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Time to Clinically Meaningful Deterioration in Function Subscale
Hide Description Participants rated their function on EORTC QLQ C-30, with total scores ranging from 0 (worst) to 100 (best); where higher score indicates better functioning. Time to deterioration was defined as the time from baseline to first 10-point (or greater) decrease as measured by physical function; to first 14-point (or greater) decrease as measured by role function, to first 7-point (or greater) decrease as measured by cognitive function. Median time to deterioration was estimated with Kaplan-Meier method. The 95% CI for the median was computed using the method of Brookmeyer and Crowley.
Time Frame From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period
Hide Outcome Measure Data
Hide Analysis Population Description
Patients of the ITT population with a baseline assessment and at least one post-treatment assessment was included in this analysis.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 191 200
Median (95% Confidence Interval)
Unit of Measure: months
Physical Function
2.79
(2.79 to 2.96)
4.86
(4.40 to 7.98)
Role Function
2.79
(2.17 to 2.89)
4.44
(4.04 to 4.53)
Cognitive Function
3.42
(3.02 to 4.24)
4.44 [1] 
(4.21 to NA)
[1]
Upper limit not reached.
11.Secondary Outcome
Title Maximum Observed Serum Concentration (Cmax) of Trastuzumab
Hide Description Only participants who received trastuzumab were to be analyzed for this outcome.
Time Frame 15-30 minutes (min) post-study treatment infusion (infusion duration = 90 min) on Day 1 of Cycle 1 and 6 (each cycle = 21 days) in neoadjuvant and adjuvant period
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic population comprised all patients who received at least one treatment dose of trastuzumab emtansine (for patients in the T-DM1 + P arm) or trastuzumab (for patients in the TCH + P arm), and had at least one post-treatment serum or plasma sample.
Arm/Group Title TCH + P
Hide Arm/Group Description:
Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).
Overall Number of Participants Analyzed 214
Mean (Standard Deviation)
Unit of Measure: micrograms per milliliter (mcg/mL)
Cycle 1 (neoadjuvant period) Number Analyzed 162 participants
167  (47.1)
Cycle 6 (neoadjuvant period) Number Analyzed 155 participants
148  (44.7)
Cycle 1 (adjuvant period) Number Analyzed 97 participants
159  (36.2)
Cycle 6 (adjuvant period) Number Analyzed 49 participants
181  (30.7)
12.Secondary Outcome
Title Cmax of Trastuzumab Emtansine and Total Trastuzumab
Hide Description Only participants who received trastuzumab emtansine were to be analyzed for this outcome.
Time Frame 15-30 min post-study treatment infusion (infusion duration = 90 min) on Day 1 of Cycle 1 and 6 (each cycle = 21 days) in neoadjuvant and adjuvant period.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic population comprised all patients who received at least one treatment dose of trastuzumab emtansine (for patients in the T-DM1 + P arm) or trastuzumab (for patients in the TCH + P arm), and had at least one post-treatment serum or plasma sample.
Arm/Group Title T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 222
Mean (Standard Deviation)
Unit of Measure: mcg/mL
Trastuzumab emtansine: C1 (neoadjuvant) Number Analyzed 207 participants
80.4  (26.5)
Trastuzumab emtansine: C6 (neoadjuvant) Number Analyzed 190 participants
71.7  (30.2)
Total Trastuzumab: C1 (neoadjuvant) Number Analyzed 208 participants
79.1  (25.7)
Total Trastuzumab: C6 (neoadjuvant) Number Analyzed 190 participants
79.1  (31.1)
Trastuzumab emtansine: C1 (adjuvant) Number Analyzed 165 participants
70.4  (22.7)
Trastuzumab emtansine: C6 (adjuvant) Number Analyzed 141 participants
73.1  (21.8)
Total Trastuzumab: C1 (adjuvant) Number Analyzed 165 participants
73.0  (23.2)
Total Trastuzumab: C6 (adjuvant) Number Analyzed 141 participants
82.6  (23.7)
13.Secondary Outcome
Title Minimum Observed Serum Concentration (Cmin) of Trastuzumab
Hide Description Only participants who received trastuzumab were to be analyzed for this outcome.
Time Frame Pre-study treatment infusion (0 hours [hr]) (infusion duration = 90 min) on Day 1 of Cycle 6 (cycle length = 21 days) in neoadjuvant and adjuvant period
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic population comprised all patients who received at least one treatment dose of trastuzumab emtansine (for patients in the T-DM1 + P arm) or trastuzumab (for patients in the TCH + P arm), and had at least one post-treatment serum or plasma sample.
Arm/Group Title TCH + P
Hide Arm/Group Description:
Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).
Overall Number of Participants Analyzed 214
Mean (Standard Deviation)
Unit of Measure: mcg/mL
Trastuzumab (neoadjuvant period) Number Analyzed 165 participants
45.8  (17.8)
Trastuzumab (adjuvant period) Number Analyzed 3 participants
21.8  (0.153)
14.Secondary Outcome
Title Cmin of Trastuzumab Emtansine and Total Trastuzumab
Hide Description Only participants who received trastuzumab emtansine were to be analyzed for this outcome.
Time Frame Pre-study treatment infusion (0 hr) (infusion duration = 90 min) on Day 1 of Cycle 6 (cycle length = 21 days) in neoadjuvant and adjuvant period
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic population comprised all patients who received at least one treatment dose of trastuzumab emtansine (for patients in the T-DM1 + P arm) or trastuzumab (for patients in the TCH + P arm), and had at least one post-treatment serum or plasma sample.
Arm/Group Title T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 222
Mean (Standard Deviation)
Unit of Measure: mcg/mL
Trastuzumab emtansine (neoadjuvant) Number Analyzed 203 participants
3.04  (7.43)
Total Trastuzumab (neoadjuvant) Number Analyzed 204 participants
12.3  (8.68)
Trastuzumab emtansine (adjuvant) Number Analyzed 149 participants
4.09  (11.7)
Total Trastuzumab (adjuvant) Number Analyzed 149 participants
8.70  (6.98)
15.Secondary Outcome
Title Plasma N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) Concentrations
Hide Description DM1 is the metabolite of trastuzumab emtansine. Only participants who received trastuzumab emtansine were to be analyzed for this outcome.
Time Frame 15-30 min post-study treatment infusion (Cmax) on Day 1 of Cycle 1 and 6 in neoadjuvant and adjuvant period
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic population comprised all patients who received at least one treatment dose of trastuzumab emtansine (for patients in the T-DM1 + P arm) or trastuzumab (for patients in the TCH + P arm), and had at least one post-treatment serum or plasma sample.
Arm/Group Title T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 222
Mean (Standard Deviation)
Unit of Measure: nanograms per milliliter (ng/mL)
C1: 15-30 min post-dose (neoadjuvant) Number Analyzed 173 participants
4.64  (2.33)
C6: 15-30 min post-dose (neoadjuvant) Number Analyzed 163 participants
4.73  (2.61)
C1: 15-30 min post-dose (adjuvant) Number Analyzed 146 participants
4.49  (2.33)
C6: 15-30 min post-dose (adjuvant) Number Analyzed 119 participants
5.15  (8.28)
16.Secondary Outcome
Title Serum Levels of Plasma DM1-Containing Catabolites Concentrations (in ng/mL) (Nonreducible Thioether Linker [MCC]-DM1 and Lysine [Lys]-MCC-DM1)
Hide Description [Not Specified]
Time Frame 15-30 min post-study treatment infusion (Cmax) on Day 1 of Cycle 1 and 6 in neoadjuvant and adjuvant period
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic population comprised all patients who received at least one treatment dose of trastuzumab emtansine (for patients in the T-DM1 + P arm) or trastuzumab (for patients in the TCH + P arm), and had at least one post-treatment serum or plasma sample.
Arm/Group Title T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 222
Mean (Standard Deviation)
Unit of Measure: ng/mL
C1: MCC-DM1 (Neoadjuvant Period) Number Analyzed 131 participants
8.18  (7.23)
C1: Lys-MCC-DM1 (Neoadjuvant period) Number Analyzed 222 participants
NA [1]   (NA)
C6: MCC-DM1 (Neoadjuvant Period) Number Analyzed 100 participants
8.22  (8.03)
C6: Lys-MCC-DM1 (Neoadjuvant period) Number Analyzed 222 participants
NA [1]   (NA)
C1: MCC-DM1 (Adjuvant Period) Number Analyzed 96 participants
7.98  (6.46)
C1: Lys-MCC-DM1 (Adjuvant period) Number Analyzed 222 participants
NA [1]   (NA)
C6: MCC-DM1 (Adjuvant Period) Number Analyzed 76 participants
7.90  (5.37)
C6: Lys-MCC-DM1 (Adjuvant period) Number Analyzed 222 participants
NA [1]   (NA)
[1]
not reported since more than 1/3 of the results are LTR (Lower than reportable)
17.Secondary Outcome
Title Percentage of Participants With ATA to Trastuzumab
Hide Description [Not Specified]
Time Frame Baseline (Pre-trastuzumab [0 hr] infusion [infusion duration = 90 min] on Day 1 of Cycle 1); post-baseline (Pre-trastuzumab infusion [0 hr] on Day 1 of Cycle 6) (each cycle = 21 days) in neoadjuvant and adjuvant period
Hide Outcome Measure Data
Hide Analysis Population Description
The participants included in this analysis were the participants who received at least one dose of trastuzumab and had at least one reported serum or plasma results.
Arm/Group Title T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 210
Measure Type: Number
Unit of Measure: Percentage of participants
Neoadjuvant Phase (baseline) Number Analyzed 210 participants
11
Neoadjuvant Phase (post-baseline) Number Analyzed 191 participants
2.6
Adjuvant Phase (baseline) Number Analyzed 129 participants
5.4
Adjuvant Phase (post-baseline) Number Analyzed 60 participants
5.0
18.Secondary Outcome
Title Percentage of Participants by Response for Hair Loss Single Item
Hide Description Participants answered the Question “Have you lost any hair?”, from the mQLQ-BR23, on a 5-point scale (1 ‘Not at all’, 2 ‘A little’, 3 'Somewhat', 4 ‘Quite a bit’, 5 ‘Very much’). Percentage of participants by each response was reported.
Time Frame Baseline,Cycle(C) 3, C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4(approx 47 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population of patients with both a baseline assessment and at least one post-treatment assessment in the respective single question are included in the analysis.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 221 223
Measure Type: Number
Unit of Measure: Percentage of Participants
Not at all: Baseline Number Analyzed 198 participants 204 participants
81.4 87.4
A little bit: Baseline Number Analyzed 198 participants 204 participants
7.7 4.0
Somewhat: Baseline Number Analyzed 198 participants 204 participants
0 0
Quite a bit: Baseline Number Analyzed 198 participants 204 participants
0.5 0
Very much: Baseline Number Analyzed 198 participants 204 participants
0 0
Not at all: Neoadjuvant Cycle 3 Number Analyzed 177 participants 183 participants
8.6 65.0
A little bit: Neoadjuvant Cycle 3 Number Analyzed 177 participants 183 participants
11.3 16.6
Somewhat: Neoadjuvant Cycle 3 Number Analyzed 177 participants 183 participants
0 0
Quite a bit: Neoadjuvant Cycle 3 Number Analyzed 177 participants 183 participants
20.8 0.4
Very much: Neoadjuvant Cycle 3 Number Analyzed 177 participants 183 participants
39.4 0
Not at all: Neoadjuvant Cycle 5 Number Analyzed 182 participants 178 participants
20.4 58.7
A little bit: Neoadjuvant Cycle 5 Number Analyzed 182 participants 178 participants
19.9 19.3
Somewhat: Neoadjuvant Cycle 5 Number Analyzed 182 participants 178 participants
0 0
Quite a bit: Neoadjuvant Cycle 5 Number Analyzed 182 participants 178 participants
15.8 1.3
Very much: Neoadjuvant Cycle 5 Number Analyzed 182 participants 178 participants
26.2 0.4
Not at all: Pre-Surgery Number Analyzed 170 participants 171 participants
30.8 49.8
A little bit: Pre-Surgery Number Analyzed 170 participants 171 participants
13.6 24.7
Somewhat: Pre-Surgery Number Analyzed 170 participants 171 participants
0 0
Quite a bit: Pre-Surgery Number Analyzed 170 participants 171 participants
11.3 2.2
Very much: Pre-Surgery Number Analyzed 170 participants 171 participants
21.3 0
Not at all: Adjuvant Cycle 4 Number Analyzed 174 participants 155 participants
67.9 50.2
A little bit: Adjuvant Cycle 4 Number Analyzed 174 participants 155 participants
5.0 15.7
Somewhat: Adjuvant Cycle 4 Number Analyzed 174 participants 155 participants
0 0
Quite a bit: Adjuvant Cycle 4 Number Analyzed 174 participants 155 participants
3.2 2.2
Very much: Adjuvant Cycle 4 Number Analyzed 174 participants 155 participants
2.7 1.3
Not at all: Adjuvant Cycle 8 Number Analyzed 168 participants 143 participants
70.1 48.9
A little bit: Adjuvant Cycle 8 Number Analyzed 168 participants 143 participants
4.1 14.3
Somewhat: Adjuvant Cycle 8 Number Analyzed 168 participants 143 participants
0 0
Quite a bit: Adjuvant Cycle 8 Number Analyzed 168 participants 143 participants
0.9 0.9
Very much: Adjuvant Cycle 8 Number Analyzed 168 participants 143 participants
0.9 0
Not at all: End of Therapy Number Analyzed 172 participants 165 participants
69.7 57.8
A little bit: End of Therapy Number Analyzed 172 participants 165 participants
5.4 14.8
Somewhat: End of Therapy Number Analyzed 172 participants 165 participants
0 0
Quite a bit: End of Therapy Number Analyzed 172 participants 165 participants
0.9 0
Very much: End of Therapy Number Analyzed 172 participants 165 participants
1.8 1.3
Not at all: Follow-up 2 Number Analyzed 150 participants 136 participants
55.7 48.4
A little bit: Follow-up 2 Number Analyzed 150 participants 136 participants
9.0 11.7
Somewhat: Follow-up 2 Number Analyzed 150 participants 136 participants
0 0
Quite a bit: Follow-up 2 Number Analyzed 150 participants 136 participants
1.4 0.4
Very much: Follow-up 2 Number Analyzed 150 participants 136 participants
1.8 0.4
Not at all: Follow-up 4 Number Analyzed 136 participants 124 participants
52.9 41.3
A little bit: Follow-up 4 Number Analyzed 136 participants 124 participants
7.2 11.2
Somewhat: Follow-up 4 Number Analyzed 136 participants 124 participants
0 0
Quite a bit: Follow-up 4 Number Analyzed 136 participants 124 participants
0 2.7
Very much: Follow-up 4 Number Analyzed 136 participants 124 participants
1.4 0.4
19.Secondary Outcome
Title Percentage of Participants With Selected Adverse Events (AEs)
Hide Description Selected AEs included hepatotoxicity, pulmonary toxicity, cardiac dysfunction, neutropenia, thrombocytopenia, peripheral neuropathy, hemorrhage, infusion related reaction (IRR)/hypersensitivity, IRR/Hypersensitivity symptoms, rash, diarrhea and mucositis. An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.
Time Frame Baseline to end of study (approximately 47 months)
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Hide Analysis Population Description
The Safety Population comprised all patients who received at least one full or partial dose of any study treatment. Patients were analyzed according to the treatment they actually received.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 219 223
Measure Type: Number
Unit of Measure: Percentage of Participants
Hepatotoxicity 14.2 39.0
Pulmonary Toxicity 0.9 4.9
Cardiac Dysfunction 4.6 1.3
Neutropenia 39.7 8.1
Thrombocytopenia 22.8 17.9
Peripheral Neuropathy 47.5 28.7
Hemorrhage 19.2 33.2
IRR/Hypersensitivity 13.7 22.9
IRR/Hypersensitivity symptoms 7.8 19.3
Rash 44.7 36.8
Diarrhea 76.7 38.6
Mucositis 43.8 24.7
20.Secondary Outcome
Title Percentage of Participants With a Clinically Meaningful Deterioration in Function Subscales
Hide Description Participants rated their function on EORTC QLQ C-30, with total score and single-item (physical, cognitive and role functioning) scores ranging from 0 (worst) to 100 (best); where higher score indicates better functioning. Clinically meaningful deterioration was defined as a decrease in score of 10 points in physical function; decrease of 7 points in cognitive function and decrease of 14 points in role function.
Time Frame From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period
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Hide Analysis Population Description
The Intent-to-treat (ITT) Population comprised all randomized participants, whether or not they received any study treatment or completed a full course of study treatment. Participants were analyzed according to their randomized treatment. As per protocol, the analysis for this outcome measure was focused on the neoadjuvant period only.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 193 205
Measure Type: Number
Unit of Measure: Percentage of Participants
Cognitive Functioning 59.1 42.4
Physical Functioning 72.5 40.0
Role Functioning 76.7 47.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TCH + P, T-DM1 + P
Comments This is the statistical analysis for cognitive functioning. 95% CI for the difference in clinically meaningful deterioration in function subscales between treatment arms was calculated using normal approximation.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Deterioration
Estimated Value -16.63
Confidence Interval (2-Sided) 95%
-26.32 to -6.94
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TCH + P, T-DM1 + P
Comments This is the statistical analysis for physical functioning. 95% CI for the difference in clinically meaningful deterioration in function subscales between treatment arms was calculated using normal approximation.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Deterioration
Estimated Value -32.54
Confidence Interval (2-Sided) 95%
-41.74 to -23.34
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection TCH + P, T-DM1 + P
Comments This is the statistical analysis for role functioning. 95% CI for the difference in clinically meaningful deterioration in function subscales between treatment arms was calculated using normal approximation.
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Deterioration
Estimated Value -28.88
Confidence Interval (2-Sided) 95%
-37.95 to -19.80
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to TDM-1
Hide Description Participants were considered post-baseline ATA positive if they had ATAs post-baseline that were either treatment-induced or treatment-enhanced. Participants had treatment-induced ATAs if they had a negative or missing ATA result at baseline, and at least one positive ATA result post-baseline. Participants had treatment-enhanced ATAs if they had a positive ATA result at baseline, and at least one positive ATA result post-baseline that was greater than or equal to (>/=) 0.60 titer units higher than the result at baseline.
Time Frame Baseline (b) (Pre-TDM1 [0 hr] infusion [infusion duration = 90 min] on Day 1 of Cycle 1); post-baseline (pb) (Pre-TDM1 infusion [0 hr] on Day 1 of Cycle 6) (each cycle = 21 days) in neoadjuvant and adjuvant period
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Hide Analysis Population Description
The participants included in this analysis were the participants who received at least one dose of trastuzumab emtansine and had at least one reported serum or plasma results.
Arm/Group Title T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 219
Measure Type: Number
Unit of Measure: Percentage of Participants
Neoadjuvant Phase (Baseline) Number Analyzed 219 participants
5.5
Neoadjuvant Phase (Post-Baseline) Number Analyzed 214 participants
7.5
Adjuvant Phase (Baseline) Number Analyzed 180 participants
11.7
Adjuvant Phase (Post-baseline) Number Analyzed 191 participants
13.1
22.Secondary Outcome
Title Percentage of Participants With a Clinically Meaningful Increase in Symptom Subscales
Hide Description Participants rated their symptoms on EORTC QLQ C-30 and mQLQ-BR23, with total scores ranging from 0 (worst) to 100 (best); where higher score indicates greater degree of symptoms. Clinically meaningful increase in symptoms was defined as an increase in score (deterioration) of 11 points in nausea and vomiting, pain, dyspnea; increase of 9 points in insomnia; increase of 14 points in appetite loss; increase of 15 points in diarrhea, constipation; increase of 10 points in fatigue, systemic therapy side effects, hair loss.
Time Frame From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) Population comprised all randomized participants, whether or not they received any study treatment or completed a full course of study treatment. Participants were analyzed according to their randomized treatment. As per protocol, the analysis for this outcome measure was focused on the neoadjuvant period only.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles).
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
Overall Number of Participants Analyzed 194 205
Measure Type: Number
Unit of Measure: Percentage of Participants
Appetite Loss 61.1 47.8
Any Hair Loss 91.2 40.5
Systemic Therapy Side-Effects 89.7 75.1
Constipation 33.2 32.7
Diarrhea 79.3 50.7
Dyspnea 56.0 31.2
Fatigue 87.6 68.8
Nausea/Vomiting 66.3 43.9
Pain 56.0 36.6
Insomnia 42.5 30.2
Time Frame From Baseline up to approximately 47 months
Adverse Event Reporting Description Safety population was analyzed.
 
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description Participants received pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion, trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 milligrams per square meter (mg/m^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter* minute (mg/mL*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles). Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
All-Cause Mortality
TCH + P T-DM1 + P
Affected / at Risk (%) Affected / at Risk (%)
Total   5/219 (2.28%)      6/223 (2.69%)    
Show Serious Adverse Events Hide Serious Adverse Events
TCH + P T-DM1 + P
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   70/219 (31.96%)      30/223 (13.45%)    
Blood and lymphatic system disorders     
Anaemia * 1  0/219 (0.00%)  0 3/223 (1.35%)  3
Febrile neutropenia * 1  26/219 (11.87%)  33 3/223 (1.35%)  3
Neutropenia * 1  7/219 (3.20%)  7 0/223 (0.00%)  0
Thrombocytopenia * 1  1/219 (0.46%)  1 1/223 (0.45%)  1
Cardiac disorders     
Cardiac failure * 1  2/219 (0.91%)  2 1/223 (0.45%)  1
Sinus tachycardia * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Left ventricular dysfunction * 1  2/219 (0.91%)  2 0/223 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Abdominal pain upper * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Colitis * 1  3/219 (1.37%)  3 0/223 (0.00%)  0
Diarrhoea * 1  9/219 (4.11%)  9 0/223 (0.00%)  0
Gastritis * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Gastrointestinal haemorrhage * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Haemorrhoids * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Ileus * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Nausea * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Small intestinal obstruction * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Stomatitis * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Vomiting * 1  4/219 (1.83%)  4 1/223 (0.45%)  1
General disorders     
Asthenia * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Pyrexia * 1  2/219 (0.91%)  2 0/223 (0.00%)  0
Non-cardiac chest pain * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Device related thrombosis * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Hepatobiliary disorders     
Nodular regenerative hyperplasia * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Immune system disorders     
Anaphylactic reaction * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Hypersensitivity * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Infections and infestations     
Bacteraemia * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Breast cellulitis * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Cellulitis * 1  2/219 (0.91%)  2 0/223 (0.00%)  0
Clostridium difficile colitis * 1  1/219 (0.46%)  2 0/223 (0.00%)  0
Clostridium difficile infection * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Device related infection * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Diarrhoea infectious * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Enterocolitis infectious * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Gastroenteritis * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Gastroenteritis norovirus * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Kidney infection * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Pneumonia * 1  2/219 (0.91%)  2 2/223 (0.90%)  2
Postoperative wound infection * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Sepsis * 1  2/219 (0.91%)  2 0/223 (0.00%)  0
Skin infection * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Subcutaneous abscess * 1  1/219 (0.46%)  1 1/223 (0.45%)  1
Upper respiratory tract infection * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Wound infection * 1  0/219 (0.00%)  0 3/223 (1.35%)  3
Breast abscess * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Injury, poisoning and procedural complications     
Subcutaneous haematoma * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Procedural intestinal perforation * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Seroma * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Investigations     
Lipase increased * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Neutrophil count decreased * 1  3/219 (1.37%)  3 0/223 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Dehydration * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Hypermagnesaemia * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Hypomagnesaemia * 1  2/219 (0.91%)  2 0/223 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Pain in extremity * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Intraductal proliferative breast lesion * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Cervix carinoma * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Neuroendocrine tumour * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Uterine leiomyoma * 1  1/219 (0.46%)  1 0/0  0
Nervous system disorders     
Headache * 1  1/219 (0.46%)  1 1/223 (0.45%)  1
Neuropathy peripheral * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Seizure * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Transient ischaemic attack * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Psychiatric disorders     
Anxiety * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Renal and urinary disorders     
Acute kidney injury * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Renal failure * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Reproductive system and breast disorders     
Adenomyosis * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Breast haematoma * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Respiratory, thoracic and mediastinal disorders     
Epistaxis * 1  0/219 (0.00%)  0 1/223 (0.45%)  3
Pleural effusion * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Pneumonitis * 1  0/219 (0.00%)  0 2/223 (0.90%)  2
Pulmonary embolism * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Respiratory failure * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Bronchiectasis * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Dyspnoea * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
Vascular disorders     
Deep vein thrombosis * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Hypertensive crisis * 1  0/219 (0.00%)  0 1/223 (0.45%)  1
Shock haemorrhagic * 1  1/219 (0.46%)  1 0/223 (0.00%)  0
1
Term from vocabulary, MedDRA 18.1
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
TCH + P T-DM1 + P
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   217/219 (99.09%)      212/223 (95.07%)    
Blood and lymphatic system disorders     
Anaemia * 1  81/219 (36.99%)  103 43/223 (19.28%)  47
Neutropenia * 1  59/219 (26.94%)  92 13/223 (5.83%)  20
Thrombocytopenia * 1  24/219 (10.96%)  36 18/223 (8.07%)  23
Eye disorders     
Dry eye * 1  14/219 (6.39%)  16 16/223 (7.17%)  16
Lacrimation increased * 1  18/219 (8.22%)  21 6/223 (2.69%)  9
Gastrointestinal disorders     
Abdominal pain * 1  30/219 (13.70%)  45 21/223 (9.42%)  29
Abdominal pain upper * 1  22/219 (10.05%)  29 7/223 (3.14%)  8
Constipation * 1  43/219 (19.63%)  48 34/223 (15.25%)  52
Diarrhoea * 1  163/219 (74.43%)  372 86/223 (38.57%)  179
Dry mouth * 1  4/219 (1.83%)  4 27/223 (12.11%)  33
Dyspepsia * 1  15/219 (6.85%)  18 25/223 (11.21%)  30
Gastrooesophageal reflux disease * 1  16/219 (7.31%)  18 7/223 (3.14%)  8
Haemorrhoids * 1  14/219 (6.39%)  19 5/223 (2.24%)  5
Nausea * 1  139/219 (63.47%)  249 103/223 (46.19%)  248
Stomatitis * 1  49/219 (22.37%)  70 23/223 (10.31%)  30
Vomiting * 1  68/219 (31.05%)  83 35/223 (15.70%)  47
Gingival bleeding * 1  1/219 (0.46%)  1 15/223 (6.73%)  17
General disorders     
Asthenia * 1  61/219 (27.85%)  115 42/223 (18.83%)  73
Chills * 1  9/219 (4.11%)  9 27/223 (12.11%)  32
Fatigue * 1  95/219 (43.38%)  143 83/223 (37.22%)  116
Influenza like illness * 1  10/219 (4.57%)  12 16/223 (7.17%)  21
Mucosal inflammation * 1  30/219 (13.70%)  37 22/223 (9.87%)  29
Oedema peripheral * 1  31/219 (14.16%)  38 10/223 (4.48%)  11
Pyrexia * 1  34/219 (15.53%)  43 38/223 (17.04%)  53
Immune system disorders     
Hypersensitivity * 1  11/219 (5.02%)  17 6/223 (2.69%)  8
Infections and infestations     
Nasopharyngitis * 1  23/219 (10.50%)  29 29/223 (13.00%)  34
Upper respiratory tract infection * 1  15/219 (6.85%)  18 21/223 (9.42%)  24
Urinary tract infection * 1  17/219 (7.76%)  20 12/223 (5.38%)  16
Injury, poisoning and procedural complications     
Radiation skin injury * 1  46/219 (21.00%)  48 21/223 (9.42%)  22
Investigations     
Alanine aminotransferase increased * 1  24/219 (10.96%)  37 64/223 (28.70%)  83
Aspartate aminotransferase increased * 1  21/219 (9.59%)  37 55/223 (24.66%)  74
Neutrophil count decreased * 1  22/219 (10.05%)  44 5/223 (2.24%)  6
Platelet count decreased * 1  26/219 (11.87%)  37 23/223 (10.31%)  38
Weight decreased * 1  24/219 (10.96%)  24 18/223 (8.07%)  19
White blood cell count decreased * 1  17/219 (7.76%)  22 8/223 (3.59%)  11
Blood bilirubin increased * 1  1/219 (0.46%)  3 20/223 (8.97%)  28
Metabolism and nutrition disorders     
Decreased appetite * 1  40/219 (18.26%)  46 33/223 (14.80%)  41
Hypokalaemia * 1  20/219 (9.13%)  23 13/223 (5.83%)  17
Hypomagnesaemia * 1  13/219 (5.94%)  13 0/223 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  41/219 (18.72%)  55 31/223 (13.90%)  37
Back pain * 1  20/219 (9.13%)  22 14/223 (6.28%)  20
Bone pain * 1  17/219 (7.76%)  25 8/223 (3.59%)  8
Muscle spasms * 1  14/219 (6.39%)  16 20/223 (8.97%)  21
Musculoskeletal pain * 1  20/219 (9.13%)  22 10/223 (4.48%)  10
Myalgia * 1  37/219 (16.89%)  41 28/223 (12.56%)  42
Pain in extremity * 1  13/219 (5.94%)  16 15/223 (6.73%)  15
Nervous system disorders     
Dizziness * 1  27/219 (12.33%)  30 22/223 (9.87%)  28
Dysgeusia * 1  44/219 (20.09%)  58 31/223 (13.90%)  39
Headache * 1  37/219 (16.89%)  53 68/223 (30.49%)  95
Hypoaesthesia * 1  19/219 (8.68%)  21 7/223 (3.14%)  9
Neuropathy peripheral * 1  29/219 (13.24%)  36 21/223 (9.42%)  37
Paraesthesia * 1  23/219 (10.50%)  28 11/223 (4.93%)  14
Peripheral sensory neuropathy * 1  26/219 (11.87%)  26 26/223 (11.66%)  27
Psychiatric disorders     
Depression * 1  16/219 (7.31%)  17 10/223 (4.48%)  10
Insomnia * 1  31/219 (14.16%)  37 36/223 (16.14%)  40
Anxiety * 1  14/219 (6.39%)  15 13/223 (5.83%)  15
Reproductive system and breast disorders     
Breast pain * 1  12/219 (5.48%)  13 17/223 (7.62%)  18
Respiratory, thoracic and mediastinal disorders     
Cough * 1  21/219 (9.59%)  26 30/223 (13.45%)  38
Dyspnoea * 1  18/219 (8.22%)  21 18/223 (8.07%)  22
Epistaxis * 1  24/219 (10.96%)  31 49/223 (21.97%)  82
Oropharyngeal pain * 1  11/219 (5.02%)  17 10/223 (4.48%)  11
Rhinorrhoea * 1  12/219 (5.48%)  16 11/223 (4.93%)  14
Skin and subcutaneous tissue disorders     
Alopecia * 1  146/219 (66.67%)  149 37/223 (16.59%)  38
Dermatitis acneiform * 1  16/219 (7.31%)  16 12/223 (5.38%)  14
Dry skin * 1  27/219 (12.33%)  32 30/223 (13.45%)  32
Nail discolouration * 1  20/219 (9.13%)  21 0/223 (0.00%)  0
Nail disorder * 1  11/219 (5.02%)  13 2/223 (0.90%)  2
Pruritus * 1  26/219 (11.87%)  34 20/223 (8.97%)  22
Rash * 1  57/219 (26.03%)  77 43/223 (19.28%)  60
Erythema * 1  8/219 (3.65%)  10 16/223 (7.17%)  18
Vascular disorders     
Hot flush * 1  45/219 (20.55%)  47 22/223 (9.87%)  25
Hypertension * 1  15/219 (6.85%)  18 14/223 (6.28%)  14
1
Term from vocabulary, MedDRA 18.1
*
Indicates events were collected by non-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: NCT02131064     History of Changes
Other Study ID Numbers: BO28408
TRIO021 ( Other Identifier: Roche )
2012-004879-38 ( EudraCT Number )
First Submitted: May 2, 2014
First Posted: May 6, 2014
Results First Submitted: December 3, 2016
Results First Posted: June 8, 2017
Last Update Posted: July 2, 2019