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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 : October 18, 2018
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 68 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 0 0
Not Completed 221 223
Reason Not Completed
Death             0             1
Lost to Follow-up             0             1
Withdrawal by Subject             6             14
Ongoing             214             207
Other             1             0
Arm/Group Title TCH + P T-DM1 + P Total
Hide Arm/Group Description Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion, trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 mg/m^2 IV infusion and carboplatin at a dose to achieve an AUC of 6 mg/mL*min IV infusion 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
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.
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
ITT population. Participants were analyzed according to their randomized treatment.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion, trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 mg/m^2 IV infusion and carboplatin at a dose to achieve an AUC of 6 mg/mL*min IV infusion 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
55.7
(48.84 to 62.32)
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 or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0155
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 -11.26
Confidence Interval (2-Sided) 95%
-20.50 to -2.02
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Event-free Survival (EFS) Assessed by Investigator Based on Radiological, Clinical and Histological Assessment
Hide Description 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.
Time Frame From randomization up to disease progression or recurrence or death (up to approximately 45 months)
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Invasive Disease-free Survival (IDFS)
Hide Description IDFS is defined only for participants who undergo surgery. Participants who do not undergo surgery will be excluded from the analysis. IDFS is defined as the time from surgery to the first documented occurrence of an IDFS event, defined as: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast 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, excluding ipsilateral invasive or local-regional breast cancer, in any anatomic site that has been either histologically confirmed or clinically diagnosed as recurrent invasive breast cancer); Contralateral invasive breast cancer; and death from any cause.
Time Frame From surgery to the first documented occurrence of IDFC event (up to approximately 45 months)
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Overall Survival
Hide Description Overall survival is defined as the time from randomization to death from any cause.
Time Frame From randomization until death (up to approximately 45 months)
Outcome Measure Data Not Reported
5.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 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
A subset of ITT population including participants who had non-inflammatory breast cancer at baseline. Participants were analyzed according to their randomized treatment.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion, trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 mg/m^2 IV infusion and carboplatin at a dose to achieve an AUC of 6 mg/mL*min IV infusion 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 or Other
Comments [Not Specified]
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]
6.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 Neoadjuvant phase (Baseline up to Cycle 6, each cycle = 21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population comprised all participants who received at least one full or partial dose of any study treatment. Participants 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 mg (loading dose) and 420 mg (maintenance dose) IV infusion, trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 mg/m^2 IV infusion and carboplatin at a dose to achieve an AUC of 6 mg/mL*min IV infusion 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 11.9 24.2
Pulmonary Toxicity 0 0.9
Cardiac Dysfunction 0.9 0.4
Neutropenia 45.2 0.9
Thrombocytopenia 21.9 7.6
Peripheral Neuropathy 30.1 9.9
Hemorrhage 14.6 20.2
IRR/Hypersensitivity 11.9 17.9
IRR/Hypersensitivity symptoms 5.9 13.9
Rash 34.7 21.5
Diarrhea 73.5 33.2
Mucositis 40.2 15.2
7.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 3, Cycle 5 of neoadjuvant period (each cycle = 21 days); pre-surgery visit (within 6 weeks after neoadjuvant therapy; up to approximately 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Participants were analyzed according to their randomized treatment. Overall number of participants analyzed = participants evaluable for this outcome measure. Number Analyzed = participants evaluable for the specified category. Percentage values are based on ITT N.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion, trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 mg/m^2 IV infusion and carboplatin at a dose to achieve an AUC of 6 mg/mL*min IV infusion 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
Not at all: Baseline Number Analyzed 194 participants 205 participants
76.9 80.7
A little bit: Baseline Number Analyzed 194 participants 205 participants
9.5 10.3
Somewhat: Baseline Number Analyzed 194 participants 205 participants
0 0
Quite a bit: Baseline Number Analyzed 194 participants 205 participants
0.9 0.9
Very much: Baseline Number Analyzed 194 participants 205 participants
0.5 0
Not at all: Cycle 3 Number Analyzed 181 participants 190 participants
55.2 61.9
A little bit: Cycle 3 Number Analyzed 181 participants 190 participants
20.8 20.2
Somewhat: Cycle 3 Number Analyzed 181 participants 190 participants
0 0
Quite a bit: Cycle 3 Number Analyzed 181 participants 190 participants
3.6 2.7
Very much: Cycle 3 Number Analyzed 181 participants 190 participants
2.3 0.4
Not at all: Cycle 5 Number Analyzed 181 participants 182 participants
37.1 55.2
A little bit: Cycle 5 Number Analyzed 181 participants 182 participants
29.9 22.0
Somewhat: Cycle 5 Number Analyzed 181 participants 182 participants
0 0
Quite a bit: Cycle 5 Number Analyzed 181 participants 182 participants
8.1 2.7
Very much: Cycle 5 Number Analyzed 181 participants 182 participants
6.8 1.8
Not at all: Pre-Surgery Number Analyzed 172 participants 176 participants
24.0 53.4
A little bit: Pre-Surgery Number Analyzed 172 participants 176 participants
28.1 18.8
Somewhat: Pre-Surgery Number Analyzed 172 participants 176 participants
0 0
Quite a bit: Pre-Surgery Number Analyzed 172 participants 176 participants
15.8 5.4
Very much: Pre-Surgery Number Analyzed 172 participants 176 participants
10.0 1.3
8.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 3, Cycle 5 of neoadjuvant period (each cycle = 21 days); pre-surgery visit (within 6 weeks after neoadjuvant therapy; up to approximately 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Participants were analyzed according to their randomized treatment. Overall number of participants analyzed = participants evaluable for this outcome measure. Number Analyzed = participants evaluable for the specified category. Percentage values are based on ITT N.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion, trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 mg/m^2 IV infusion and carboplatin at a dose to achieve an AUC of 6 mg/mL*min IV infusion 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
Question 1: Not at all: Baseline Number Analyzed 193 participants 205 participants
70.6 72.6
Question 1: A little bit: Baseline Number Analyzed 193 participants 205 participants
14.5 16.6
Question 1: Somewhat: Baseline Number Analyzed 193 participants 205 participants
0 0
Question 1: Quite a bit: Baseline Number Analyzed 193 participants 205 participants
2.3 2.2
Question 1: Very much: Baseline Number Analyzed 193 participants 205 participants
0 0.4
Question 1: Not at all: Cycle 3 Number Analyzed 180 participants 190 participants
35.3 50.7
Question 1: A little bit: Cycle 3 Number Analyzed 180 participants 190 participants
32.1 28.3
Question 1: Somewhat: Cycle 3 Number Analyzed 180 participants 190 participants
0 0
Question 1: Quite a bit: Cycle 3 Number Analyzed 180 participants 190 participants
11.8 4.5
Question 1: Very much: Cycle 3 Number Analyzed 180 participants 190 participants
2.3 1.8
Question 1: Not at all: Cycle 5 Number Analyzed 180 participants 182 participants
48.9 48.0
Question 1: A little bit: Cycle 5 Number Analyzed 180 participants 182 participants
22.6 25.6
Question 1: Somewhat: Cycle 5 Number Analyzed 180 participants 182 participants
0 0
Question 1: Quite a bit: Cycle 5 Number Analyzed 180 participants 182 participants
7.7 6.7
Question 1: Very much: Cycle 5 Number Analyzed 180 participants 182 participants
2.3 1.3
Question 1: Not at all: Pre-Surgery Number Analyzed 172 participants 176 participants
40.7 49.3
Question 1: A little bit: Pre-Surgery Number Analyzed 172 participants 176 participants
27.1 22.4
Question 1: Somewhat: Pre-Surgery Number Analyzed 172 participants 176 participants
0 0
Question 1: Quite a bit: Pre-Surgery Number Analyzed 172 participants 176 participants
7.7 5.8
Question 1: Very much: Pre-Surgery Number Analyzed 172 participants 176 participants
2.3 1.3
Question 2: Not at all: Baseline Number Analyzed 194 participants 205 participants
64.3 66.8
Question 2: A little bit: Baseline Number Analyzed 194 participants 205 participants
19.9 18.4
Question 2: Somewhat: Baseline Number Analyzed 194 participants 205 participants
0 0
Question 2: Quite a bit: Baseline Number Analyzed 194 participants 205 participants
3.2 6.3
Question 2: Very much: Baseline Number Analyzed 194 participants 205 participants
0.5 0.4
Question 2: Not at all: Cycle 3 Number Analyzed 181 participants 190 participants
13.6 25.1
Question 2: A little bit: Cycle 3 Number Analyzed 181 participants 190 participants
40.7 40.4
Question 2: Somewhat: Cycle 3 Number Analyzed 181 participants 190 participants
0 0
Question 2: Quite a bit: Cycle 3 Number Analyzed 181 participants 190 participants
20.4 15.2
Question 2: Very much: Cycle 3 Number Analyzed 181 participants 190 participants
7.2 4.5
Question 2: Not at all: Cycle 5 Number Analyzed 181 participants 182 participants
21.3 26.9
Question 2: A little bit: Cycle 5 Number Analyzed 181 participants 182 participants
35.7 37.2
Question 2: Somewhat: Cycle 5 Number Analyzed 181 participants 182 participants
0 0
Question 2: Quite a bit: Cycle 5 Number Analyzed 181 participants 182 participants
19.9 13.5
Question 2: Very much: Cycle 5 Number Analyzed 181 participants 182 participants
5.0 4.0
Question 2: Not at all: Pre-Surgery Number Analyzed 172 participants 176 participants
20.8 28.7
Question 2: A little bit: Pre-Surgery Number Analyzed 172 participants 176 participants
33.9 37.2
Question 2: Somewhat: Pre-Surgery Number Analyzed 172 participants 176 participants
0 0
Question 2: Quite a bit: Pre-Surgery Number Analyzed 172 participants 176 participants
16.7 9.0
Question 2: Very much: Pre-Surgery Number Analyzed 172 participants 176 participants
6.3 4.0
9.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 3, Cycle 5 of neoadjuvant period (each cycle = 21 days); pre-surgery visit (within 6 weeks after neoadjuvant therapy; up to approximately 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Participants were analyzed according to their randomized treatment. Overall number of participants analyzed = participants evaluable for this outcome measure. Number Analyzed = participants evaluable for the specified category. Percentage values are based on ITT N.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion, trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 mg/m^2 IV infusion and carboplatin at a dose to achieve an AUC of 6 mg/mL*min IV infusion 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
Not at all: Baseline Number Analyzed 194 participants 205 participants
79.6 87.4
A little bit: Baseline Number Analyzed 194 participants 205 participants
7.7 4.5
Somewhat: Baseline Number Analyzed 194 participants 205 participants
0 0
Quite a bit: Baseline Number Analyzed 194 participants 205 participants
0.5 0
Very much: Baseline Number Analyzed 194 participants 205 participants
0 0
Not at all: Cycle 3 Number Analyzed 181 participants 190 participants
8.6 67.3
A little bit: Cycle 3 Number Analyzed 181 participants 190 participants
11.8 17.5
Somewhat: Cycle 3 Number Analyzed 181 participants 190 participants
0 0
Quite a bit: Cycle 3 Number Analyzed 181 participants 190 participants
20.8 0.4
Very much: Cycle 3 Number Analyzed 181 participants 190 participants
40.7 0
Not at all: Cycle 5 Number Analyzed 181 participants 182 participants
20.4 59.2
A little bit: Cycle 5 Number Analyzed 181 participants 182 participants
19.9 20.2
Somewhat: Cycle 5 Number Analyzed 181 participants 182 participants
0 0
Quite a bit: Cycle 5 Number Analyzed 181 participants 182 participants
15.4 1.8
Very much: Cycle 5 Number Analyzed 181 participants 182 participants
26.2 0.4
Not at all: Pre-Surgery Number Analyzed 172 participants 176 participants
31.7 51.6
A little bit: Pre-Surgery Number Analyzed 172 participants 176 participants
12.7 25.1
Somewhat: Pre-Surgery Number Analyzed 172 participants 176 participants
0 0
Quite a bit: Pre-Surgery Number Analyzed 172 participants 176 participants
11.3 2.2
Very much: Pre-Surgery Number Analyzed 172 participants 176 participants
22.2 0
10.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
ITT population. Participants were analyzed according to their randomized treatment. Overall number of participants analyzed = Number of participants evaluable for this outcome measure.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion, trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 mg/m^2 IV infusion and carboplatin at a dose to achieve an AUC of 6 mg/mL*min IV infusion 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 or Other
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]
11.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
ITT population. Participants were analyzed according to their randomized treatment. Overall number of participants analyzed = Number of participants evaluable for this outcome measure.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion, trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 mg/m^2 IV infusion and carboplatin at a dose to achieve an AUC of 6 mg/mL*min IV infusion 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 or Other
Comments [Not Specified]
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]
12.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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ITT population. Participants were analyzed according to their randomized treatment. Overall number of participants analyzed = Number of participants evaluable for this outcome measure.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion, trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 mg/m^2 IV infusion and carboplatin at a dose to achieve an AUC of 6 mg/mL*min IV infusion 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 or Other
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 or Other
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 or Other
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]
13.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
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ITT population. Participants were analyzed according to their randomized treatment. Overall number of participants analyzed = Number of participants evaluable for this outcome measure.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion, trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 mg/m^2 IV infusion and carboplatin at a dose to achieve an AUC of 6 mg/mL*min IV infusion 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]
Here, NA represents data not estimable.
14.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
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Hide Analysis Population Description
ITT population. Participants were analyzed according to their randomized treatment. Overall number of participants analyzed = Number of participants evaluable for this outcome measure. Number Analyzed = participants evaluable for the specified category.
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description:
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion, trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 mg/m^2 IV infusion and carboplatin at a dose to achieve an AUC of 6 mg/mL*min IV infusion 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 Number Analyzed 193 participants 205 participants
61.1 47.8
Any Hair Loss Number Analyzed 194 participants 205 participants
91.2 40.5
Systemic Therapy Side-Effects Number Analyzed 194 participants 205 participants
89.7 75.1
Constipation Number Analyzed 193 participants 205 participants
33.2 32.7
Diarrhea Number Analyzed 193 participants 205 participants
79.3 50.7
Dyspnea Number Analyzed 193 participants 205 participants
56.0 31.2
Fatigue Number Analyzed 193 participants 205 participants
87.6 68.8
Nausea/Vomiting Number Analyzed 193 participants 205 participants
66.3 43.9
Pain Number Analyzed 193 participants 205 participants
56.0 36.6
Insomnia Number Analyzed 193 participants 205 participants
42.5 30.2
15.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 period
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Hide Analysis Population Description
Pharmacokinetic (PK) population:all participants who received at least one dose of T-DM1 (in T-DM1 + P arm) or TCH (in TCH + P arm), and had at least one post-treatment serum sample. Overall number of participants analyzed=Participants in PK Population evaluable for this outcome. Number Analyzed=participants evaluable for specified category.
Arm/Group Title TCH + P
Hide Arm/Group Description:
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion, trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 mg/m^2 IV infusion and carboplatin at a dose to achieve an AUC of 6 mg/mL*min IV infusion 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 162
Mean (Standard Deviation)
Unit of Measure: micrograms per milliliter (mcg/mL)
Cycle 1 Number Analyzed 162 participants
167  (47.1)
Cycle 6 Number Analyzed 155 participants
148  (44.7)
16.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 period
Hide Outcome Measure Data
Hide Analysis Population Description
PK population. Overall number of participants analyzed = Participants in PK Population evaluable for this outcome measure. Number Analyzed = participants evaluable for specified category.
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 207
Mean (Standard Deviation)
Unit of Measure: mcg/mL
Trastuzumab emtansine: Cycle 1 Number Analyzed 206 participants
80.3  (26.6)
Trastuzumab emtansine: Cycle 6 Number Analyzed 179 participants
72.3  (30.0)
Total Trastuzumab: Cycle 1 Number Analyzed 207 participants
79.0  (25.7)
Total Trastuzumab: Cycle 6 Number Analyzed 179 participants
79.5  (30.9)
17.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 period
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Hide Analysis Population Description
PK population. Overall number of participants analyzed = Number of participants in PK Population with evaluable samples at a given timepoint.
Arm/Group Title TCH + P
Hide Arm/Group Description:
Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion, trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 mg/m^2 IV infusion and carboplatin at a dose to achieve an AUC of 6 mg/mL*min IV infusion 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 165
Mean (Standard Deviation)
Unit of Measure: mcg/mL
45.8  (17.8)
18.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 period
Hide Outcome Measure Data
Hide Analysis Population Description
PK population. Overall number of participants analyzed = Participants in PK Population evaluable for this outcome measure. Number Analyzed = participants evaluable for specified category.
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 191
Mean (Standard Deviation)
Unit of Measure: mcg/mL
Trastuzumab emtansine Number Analyzed 190 participants
3.06  (7.68)
Total Trastuzumab Number Analyzed 191 participants
12.5  (8.90)
19.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 Pre-study treatment infusion (0 hr) (infusion duration = 90 min) on Day 1 of Cycle 1 (cycle length = 21 days); 15-30 min post-study treatment infusion on Day 1 of Cycle 1 and 6 in neoadjuvant period
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Hide Analysis Population Description
PK population. Overall number of participants analyzed = Participants in PK Population evaluable for this outcome measure. Number Analyzed = participants evaluable for specified category.
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 211
Mean (Standard Deviation)
Unit of Measure: nanograms per milliliter (ng/mL)
Cycle 1: Pre-dose Number Analyzed 211 participants
0.0841  (0.881)
Cycle 1: 15-30 min post-dose Number Analyzed 209 participants
4.98  (2.82)
Cycle 6: 15-30 min post-dose Number Analyzed 180 participants
4.85  (2.74)
20.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 Pre-study treatment infusion (0 hr) (infusion duration = 90 min) on Day 1 of Cycle 1 (cycle length = 21 days) in neoadjuvant period; 15-30 min post-study treatment infusion on Day 1 of Cycle 1 and 6 in neoadjuvant and adjuvant period
Outcome Measure Data Not Reported
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 (Pre-TDM1 [0 hr] infusion [infusion duration = 90 min] on Day 1 of Cycle 1); post-baseline (Pre-TDM1 infusion [0 hr] on Day 1 of Cycle 6) (each cycle = 21 days) in neoadjuvant period
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population, including participants from T-DM1 + P arm only. Overall number of participants analyzed = participants evaluable for this outcome measure. Number Analyzed = participants evaluable for the specified category.
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 216
Measure Type: Number
Unit of Measure: percentage of participants
Neoadjuvant Phase: At Baseline Number Analyzed 216 participants
5.6
Neoadjuvant Phase: At Post-Baseline Number Analyzed 201 participants
8.0
22.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
Outcome Measure Data Not Reported
Time Frame From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period
Adverse Event Reporting Description Safety population was analyzed.
 
Arm/Group Title TCH + P T-DM1 + P
Hide Arm/Group Description Participants received pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion, trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion, docetaxel 75 mg/m^2 IV infusion and carboplatin at a dose to achieve an AUC of 6 mg/mL*min IV infusion 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   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
TCH + P T-DM1 + P
Affected / at Risk (%) Affected / at Risk (%)
Total   63/219 (28.77%)   11/223 (4.93%) 
Blood and lymphatic system disorders     
Anaemia * 1  0/219 (0.00%)  3/223 (1.35%) 
Febrile neutropenia * 1  26/219 (11.87%)  3/223 (1.35%) 
Neutropenia * 1  7/219 (3.20%)  0/223 (0.00%) 
Thrombocytopenia * 1  1/219 (0.46%)  1/223 (0.45%) 
Cardiac disorders     
Cardiac failure * 1  2/219 (0.91%)  1/223 (0.45%) 
Sinus tachycardia * 1  1/219 (0.46%)  0/223 (0.00%) 
Gastrointestinal disorders     
Abdominal pain * 1  1/219 (0.46%)  0/223 (0.00%) 
Abdominal pain upper * 1  1/219 (0.46%)  0/223 (0.00%) 
Colitis * 1  3/219 (1.37%)  0/223 (0.00%) 
Diarrhoea * 1  9/219 (4.11%)  0/223 (0.00%) 
Gastritis * 1  0/219 (0.00%)  1/223 (0.45%) 
Gastrointestinal haemorrhage * 1  1/219 (0.46%)  0/223 (0.00%) 
Haemorrhoids * 1  1/219 (0.46%)  0/223 (0.00%) 
Ileus * 1  0/219 (0.00%)  1/223 (0.45%) 
Nausea * 1  1/219 (0.46%)  0/223 (0.00%) 
Small intestinal obstruction * 1  1/219 (0.46%)  0/223 (0.00%) 
Stomatitis * 1  1/219 (0.46%)  0/223 (0.00%) 
Vomiting * 1  4/219 (1.83%)  1/223 (0.45%) 
General disorders     
Asthenia * 1  1/219 (0.46%)  0/223 (0.00%) 
Pyrexia * 1  2/219 (0.91%)  0/223 (0.00%) 
Immune system disorders     
Anaphylactic reaction * 1  1/219 (0.46%)  0/223 (0.00%) 
Hypersensitivity * 1  1/219 (0.46%)  0/223 (0.00%) 
Infections and infestations     
Bacteraemia * 1  0/219 (0.00%)  1/223 (0.45%) 
Breast cellulitis * 1  0/219 (0.00%)  1/223 (0.45%) 
Cellulitis * 1  2/219 (0.91%)  0/223 (0.00%) 
Clostridium difficile colitis * 1  1/219 (0.46%)  0/223 (0.00%) 
Clostridium difficile infection * 1  1/219 (0.46%)  0/223 (0.00%) 
Device related infection * 1  1/219 (0.46%)  0/223 (0.00%) 
Diarrhoea infectious * 1  1/219 (0.46%)  0/223 (0.00%) 
Enterocolitis infectious * 1  1/219 (0.46%)  0/223 (0.00%) 
Gastroenteritis * 1  1/219 (0.46%)  0/223 (0.00%) 
Gastroenteritis norovirus * 1  1/219 (0.46%)  0/223 (0.00%) 
Kidney infection * 1  1/219 (0.46%)  0/223 (0.00%) 
Pneumonia * 1  2/219 (0.91%)  2/223 (0.90%) 
Postoperative wound infection * 1  1/219 (0.46%)  0/223 (0.00%) 
Sepsis * 1  2/219 (0.91%)  0/223 (0.00%) 
Skin infection * 1  0/219 (0.00%)  1/223 (0.45%) 
Subcutaneous abscess * 1  1/219 (0.46%)  0/223 (0.00%) 
Upper respiratory tract infection * 1  1/219 (0.46%)  0/223 (0.00%) 
Wound infection * 1  0/219 (0.00%)  2/223 (0.90%) 
Injury, poisoning and procedural complications     
Subcutaneous haematoma * 1  1/219 (0.46%)  0/223 (0.00%) 
Procedural intestinal perforation * 1  1/219 (0.46%)  0/223 (0.00%) 
Investigations     
Ejection fraction decreased * 1  1/219 (0.46%)  0/223 (0.00%) 
Lipase increased * 1  0/219 (0.00%)  1/223 (0.45%) 
Neutrophil count decreased * 1  3/219 (1.37%)  0/223 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  1/219 (0.46%)  0/223 (0.00%) 
Dehydration * 1  1/219 (0.46%)  0/223 (0.00%) 
Hypermagnesaemia * 1  1/219 (0.46%)  0/223 (0.00%) 
Hypomagnesaemia * 1  2/219 (0.91%)  0/223 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Intraductal proliferative breast lesion * 1  0/219 (0.00%)  1/223 (0.45%) 
Nervous system disorders     
Headache * 1  1/219 (0.46%)  1/223 (0.45%) 
Neuropathy peripheral * 1  0/219 (0.00%)  1/223 (0.45%) 
Seizure * 1  0/219 (0.00%)  1/223 (0.45%) 
Transient ischaemic attack * 1  1/219 (0.46%)  0/223 (0.00%) 
Psychiatric disorders     
Anxiety * 1  0/219 (0.00%)  1/223 (0.45%) 
Renal and urinary disorders     
Acute kidney injury * 1  0/219 (0.00%)  1/223 (0.45%) 
Renal failure * 1  1/219 (0.46%)  0/223 (0.00%) 
Reproductive system and breast disorders     
Adenomyosis * 1  1/219 (0.46%)  0/223 (0.00%) 
Breast haematoma * 1  0/219 (0.00%)  1/223 (0.45%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis * 1  0/219 (0.00%)  1/223 (0.45%) 
Pleural effusion * 1  1/219 (0.46%)  0/223 (0.00%) 
Pneumonitis * 1  0/219 (0.00%)  2/223 (0.90%) 
Pulmonary embolism * 1  1/219 (0.46%)  0/223 (0.00%) 
Respiratory failure * 1  0/219 (0.00%)  1/223 (0.45%) 
Vascular disorders     
Deep vein thrombosis * 1  0/219 (0.00%)  1/223 (0.45%) 
Hypertensive crisis * 1  0/219 (0.00%)  1/223 (0.45%) 
Shock haemorrhagic * 1  1/219 (0.46%)  0/223 (0.00%) 
Thrombophlebitis superficial * 1  1/219 (0.46%)  0/223 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.1
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 (%) Affected / at Risk (%)
Total   215/219 (98.17%)   198/223 (88.79%) 
Blood and lymphatic system disorders     
Anaemia * 1  78/219 (35.62%)  30/223 (13.45%) 
Neutropenia * 1  58/219 (26.48%)  9/223 (4.04%) 
Thrombocytopenia * 1  21/219 (9.59%)  16/223 (7.17%) 
Eye disorders     
Dry eye * 1  11/219 (5.02%)  14/223 (6.28%) 
Lacrimation increased * 1  17/219 (7.76%)  4/223 (1.79%) 
Gastrointestinal disorders     
Abdominal pain * 1  29/219 (13.24%)  18/223 (8.07%) 
Abdominal pain upper * 1  18/219 (8.22%)  4/223 (1.79%) 
Constipation * 1  39/219 (17.81%)  25/223 (11.21%) 
Diarrhoea * 1  159/219 (72.60%)  83/223 (37.22%) 
Dry mouth * 1  2/219 (0.91%)  23/223 (10.31%) 
Dyspepsia * 1  15/219 (6.85%)  22/223 (9.87%) 
Gastrooesophageal reflux disease * 1  15/219 (6.85%)  7/223 (3.14%) 
Haemorrhoids * 1  14/219 (6.39%)  4/223 (1.79%) 
Nausea * 1  132/219 (60.27%)  95/223 (42.60%) 
Stomatitis * 1  47/219 (21.46%)  21/223 (9.42%) 
Vomiting * 1  68/219 (31.05%)  29/223 (13.00%) 
General disorders     
Asthenia * 1  57/219 (26.03%)  39/223 (17.49%) 
Chills * 1  9/219 (4.11%)  23/223 (10.31%) 
Fatigue * 1  93/219 (42.47%)  74/223 (33.18%) 
Influenza like illness * 1  6/219 (2.74%)  13/223 (5.83%) 
Mucosal inflammation * 1  30/219 (13.70%)  18/223 (8.07%) 
Oedema peripheral * 1  27/219 (12.33%)  5/223 (2.24%) 
Pyrexia * 1  29/219 (13.24%)  30/223 (13.45%) 
Infections and infestations     
Nasopharyngitis * 1  15/219 (6.85%)  22/223 (9.87%) 
Upper respiratory tract infection * 1  9/219 (4.11%)  16/223 (7.17%) 
Urinary tract infection * 1  14/219 (6.39%)  9/223 (4.04%) 
Injury, poisoning and procedural complications     
Radiation skin injury * 1  20/219 (9.13%)  9/223 (4.04%) 
Investigations     
Alanine aminotransferase increased * 1  23/219 (10.50%)  52/223 (23.32%) 
Aspartate aminotransferase increased * 1  18/219 (8.22%)  39/223 (17.49%) 
Neutrophil count decreased * 1  22/219 (10.05%)  4/223 (1.79%) 
Platelet count decreased * 1  27/219 (12.33%)  13/223 (5.83%) 
Weight decreased * 1  22/219 (10.05%)  13/223 (5.83%) 
White blood cell count decreased * 1  15/219 (6.85%)  4/223 (1.79%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  39/219 (17.81%)  26/223 (11.66%) 
Hypokalaemia * 1  20/219 (9.13%)  10/223 (4.48%) 
Hypomagnesaemia * 1  11/219 (5.02%)  0/223 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  30/219 (13.70%)  19/223 (8.52%) 
Back pain * 1  17/219 (7.76%)  8/223 (3.59%) 
Bone pain * 1  14/219 (6.39%)  4/223 (1.79%) 
Muscle spasms * 1  7/219 (3.20%)  12/223 (5.38%) 
Musculoskeletal pain * 1  12/219 (5.48%)  7/223 (3.14%) 
Myalgia * 1  29/219 (13.24%)  26/223 (11.66%) 
Nervous system disorders     
Dizziness * 1  25/219 (11.42%)  18/223 (8.07%) 
Dysgeusia * 1  43/219 (19.63%)  30/223 (13.45%) 
Headache * 1  35/219 (15.98%)  62/223 (27.80%) 
Hypoaesthesia * 1  14/219 (6.39%)  5/223 (2.24%) 
Neuropathy peripheral * 1  27/219 (12.33%)  15/223 (6.73%) 
Paraesthesia * 1  19/219 (8.68%)  4/223 (1.79%) 
Peripheral sensory neuropathy * 1  22/219 (10.05%)  16/223 (7.17%) 
Psychiatric disorders     
Depression * 1  14/219 (6.39%)  8/223 (3.59%) 
Insomnia * 1  29/219 (13.24%)  32/223 (14.35%) 
Reproductive system and breast disorders     
Breast pain * 1  9/219 (4.11%)  15/223 (6.73%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  15/219 (6.85%)  26/223 (11.66%) 
Dyspnoea * 1  14/219 (6.39%)  13/223 (5.83%) 
Epistaxis * 1  24/219 (10.96%)  35/223 (15.70%) 
Oropharyngeal pain * 1  11/219 (5.02%)  7/223 (3.14%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  142/219 (64.84%)  31/223 (13.90%) 
Dermatitis acneiform * 1  13/219 (5.94%)  7/223 (3.14%) 
Dry skin * 1  23/219 (10.50%)  27/223 (12.11%) 
Nail discolouration * 1  14/219 (6.39%)  0/223 (0.00%) 
Nail disorder * 1  14/219 (6.39%)  6/223 (2.69%) 
Pruritus * 1  16/219 (7.31%)  13/223 (5.83%) 
Rash * 1  54/219 (24.66%)  42/223 (18.83%) 
Vascular disorders     
Hot flush * 1  30/219 (13.70%)  17/223 (7.62%) 
Hypertension * 1  14/219 (6.39%)  10/223 (4.48%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor’s intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: 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: October 18, 2018