Trial Outcomes & Findings for 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 (NCT NCT02131064)

Last Updated: 2019-07-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

444 participants

Primary outcome timeframe

Pre-surgery (within 6 weeks after neoadjuvant therapy; up to approximately 6 months)

Results posted on

2019-07-02

Participant Flow

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)

Participant milestones

Participant milestones
Measure	TCH + P 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).	T-DM1 + P 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 Study STARTED	221	223
Overall Study COMPLETED	196	189
Overall Study NOT COMPLETED	25	34

Reasons for withdrawal

Reasons for withdrawal
Measure	TCH + P 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).	T-DM1 + P 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 Study Death	5	6
Overall Study Lost to Follow-up	4	8
Overall Study Withdrawal by Subject	14	18
Overall Study Other	2	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TCH + P n=221 Participants 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).	T-DM1 + P n=223 Participants 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 n=444 Participants Total of all reporting groups
Age, Continuous	49.3 years STANDARD_DEVIATION 11.2 • n=5 Participants	50.5 years STANDARD_DEVIATION 10.6 • n=7 Participants	49.9 years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	221 Participants n=5 Participants	222 Participants n=7 Participants	443 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-surgery (within 6 weeks after neoadjuvant therapy; up to approximately 6 months)

Population: 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.

Outcome measures

Outcome measures
Measure	TCH + P n=221 Participants 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).	T-DM1 + P n=223 Participants 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).
Percentage of Participants With Total Pathological Complete Response (tpCR) Assessed Based on Tumor Samples	56.1 Percentage of Participants Interval 49.29 to 62.76	44.4 Percentage of Participants Interval 37.76 to 51.18

SECONDARY outcome

Timeframe: From randomization until death (up to approximately 47 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	TCH + P n=221 Participants 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).	T-DM1 + P n=223 Participants 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 Survival	97.6 Probability Interval 95.5 to 99.7	97.0 Probability Interval 94.6 to 99.4

SECONDARY outcome

Timeframe: Surgery performed after completion of neoadjuvant therapy (approximately 6 months after neoadjuvant period)

BCS rate was defined as the percentage of participants who achieve BCS out of the ITT population of participants without inflammatory breast cancer.

Outcome measures

Outcome measures
Measure	TCH + P n=213 Participants 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).	T-DM1 + P n=218 Participants 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).
Percentage of Participants Who Received Breast-Conserving Surgery (BCS)	52.6 Percentage of Participants 95% Confidence Interval 45.65 • Interval 45.65 to 59.45	41.7 Percentage of Participants 95% Confidence Interval 35.12 • Interval 35.12 to 48.33

SECONDARY outcome

Timeframe: From randomization up to disease progression or recurrence or death (up to approximately 47 months)

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.

Outcome measures

Outcome measures
Measure	TCH + P n=221 Participants 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).	T-DM1 + P n=223 Participants 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).
Event-Free Survival	94.21 Probability Interval 91.02 to 97.39	85.28 Probability Interval 80.47 to 90.08

SECONDARY outcome

Timeframe: From surgery to the first documented occurrence of IDFC event (up to approximately 47 months)

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.

Outcome measures

Outcome measures
Measure	TCH + P n=221 Participants 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).	T-DM1 + P n=223 Participants 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).
Invasive Disease-free Survival (IDFS)	91.99 Probability Interval 86.73 to 97.26	93.04 Probability Interval 89.39 to 96.69

SECONDARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	TCH + P n=221 Participants 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).	T-DM1 + P n=223 Participants 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).
Percentage of Participants by Response for Neuropathy Single Item A little bit: Pre-Surgery	29.0 Percentage of Participants	17.9 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Somewhat: Pre-Surgery	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Not at all: Neoadjuvant Cycle 3	54.3 Percentage of Participants	59.6 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item A little bit: Neoadjuvant Cycle 3	20.8 Percentage of Participants	19.3 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Somewhat: Neoadjuvant Cycle 3	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Quite a bit: Neoadjuvant Cycle 3	3.2 Percentage of Participants	2.7 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Very much: Neoadjuvant Cycle 3	1.8 Percentage of Participants	0.4 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Not at all: Neoadjuvant Cycle 5	37.1 Percentage of Participants	54.3 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item A little bit: Neoadjuvant Cycle 5	29.9 Percentage of Participants	21.1 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Somewhat: Neoadjuvant Cycle 5	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Quite a bit: Neoadjuvant Cycle 5	8.6 Percentage of Participants	2.7 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Very much: Neoadjuvant Cycle 5	6.8 Percentage of Participants	1.8 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Not at all: Pre-Surgery	22.6 Percentage of Participants	52.0 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Quite a bit: Pre-Surgery	15.4 Percentage of Participants	5.4 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Very much: Pre-Surgery	10.0 Percentage of Participants	1.3 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Not at all: Adjuvant Cycle 4	31.2 Percentage of Participants	42.6 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item A little bit: Adjuvant Cycle 4	31.7 Percentage of Participants	15.2 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Somewhat: Adjuvant Cycle 4	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Quite a bit: Adjuvant Cycle 4	9.5 Percentage of Participants	9.0 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Very much: Adjuvant Cycle 4	6.3 Percentage of Participants	2.7 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Not at all: Adjuvant Cycle 8	33.0 Percentage of Participants	31.8 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item A little bit: Adjuvant Cycle 8	28.1 Percentage of Participants	19.3 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Somewhat: Adjuvant Cycle 8	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Quite a bit: Adjuvant Cycle 8	10.9 Percentage of Participants	9.0 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Very much: Adjuvant Cycle 8	4.1 Percentage of Participants	4.0 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Not at all: End of Therapy	31.2 Percentage of Participants	31.4 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item A little bit: End of Therapy	30.8 Percentage of Participants	23.8 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Somewhat: End of Therapy	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Quite a bit: End of Therapy	10.9 Percentage of Participants	12.1 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Very much: End of Therapy	5.0 Percentage of Participants	6.7 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Not at all: Follow-up 2	38.0 Percentage of Participants	32.7 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item A little bit: Follow-up 2	19.9 Percentage of Participants	19.3 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Somewhat: Follow-up 2	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Quite a bit: Follow-up 2	5.9 Percentage of Participants	7.6 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Very much: Follow-up 2	4.1 Percentage of Participants	1.3 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Not at all: Follow-up 4	39.8 Percentage of Participants	32.7 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item A little bit: Follow-up 4	15.4 Percentage of Participants	17.9 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Somewhat: Follow-up 4	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Quite a bit: Follow-up 4	4.1 Percentage of Participants	3.1 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Very much: Follow-up 4	2.3 Percentage of Participants	1.8 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Not at all: Baseline	78.7 Percentage of Participants	81.2 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item A little bit: Baseline	9.5 Percentage of Participants	9.4 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Somewhat: Baseline	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Quite a bit: Baseline	0.9 Percentage of Participants	0.9 Percentage of Participants
Percentage of Participants by Response for Neuropathy Single Item Very much: Baseline	0.5 Percentage of Participants	0 Percentage of Participants

SECONDARY outcome

Population: 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.

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.

Outcome measures

Outcome measures
Measure	TCH + P n=221 Participants 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).	T-DM1 + P n=223 Participants 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).
Percentage of Participants by Response for Skin Problem Single Items Q2: Somewhat: Follow-up 4	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Not at all: Baseline	71.9 Percentage of Participants	72.6 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: A little bit: Baseline	14.9 Percentage of Participants	16.1 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Somewhat: Baseline	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Quite a bit: Baseline	2.3 Percentage of Participants	2.2 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Very much: Baseline	0 Percentage of Participants	0.4 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Not at all: Neoadjuvant Cycle 3	35.3 Percentage of Participants	48.9 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: A little bit: Neoadjuvant Cycle 3	31.2 Percentage of Participants	27.4 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Somewhat: Neoadjuvant Cycle 3	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Quite a bit: Neoadjuvant Cycle 3	10.9 Percentage of Participants	4.0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Very much: Neoadjuvant Cycle 3	2.3 Percentage of Participants	1.8 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Not at all: Neoadjuvant Cycle 5	48.9 Percentage of Participants	46.2 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: A little bit: Neoadjuvant Cycle 5	23.1 Percentage of Participants	26.0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Somewhat: Neoadjuvant Cycle 5	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Quite a bit: Neoadjuvant Cycle 5	7.7 Percentage of Participants	6.3 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Very much: Neoadjuvant Cycle 5	2.3 Percentage of Participants	1.3 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Not at all: Pre-Surgery	40.3 Percentage of Participants	48.0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: A little bit: Pre-Surgery	26.7 Percentage of Participants	21.5 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Somewhat: Pre-Surgery	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Quite a bit: Pre-Surgery	7.2 Percentage of Participants	5.8 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Very much: Pre-Surgery	2.7 Percentage of Participants	1.3 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Not at all: Adjuvant Cycle 4	38.5 Percentage of Participants	39.0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: A little bit: Adjuvant Cycle 4	23.5 Percentage of Participants	21.5 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Somewhat: Adjuvant Cycle 4	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Quite a bit: Adjuvant Cycle 4	9.5 Percentage of Participants	6.7 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Very much: Adjuvant Cycle 4	6.8 Percentage of Participants	2.2 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Not at all: Adjuvant Cycle 8	34.8 Percentage of Participants	39.0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: A little bit: Adjuvant Cycle 8	27.6 Percentage of Participants	15.7 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Somewhat: Adjuvant Cycle 8	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Quite a bit: Adjuvant Cycle 8	9.0 Percentage of Participants	6.3 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Very much: Adjuvant Cycle 8	4.1 Percentage of Participants	3.1 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Not at all: End of Therapy	39.4 Percentage of Participants	42.6 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: A little bit: End of Therapy	26.7 Percentage of Participants	22.9 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Somewhat: End of Therapy	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Quite a bit: End of Therapy	6.8 Percentage of Participants	6.7 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Very much: End of Therapy	4.5 Percentage of Participants	1.8 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Not at all: Follow-up 2	43.9 Percentage of Participants	39.9 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: A little bit: Follow-up 2	19.0 Percentage of Participants	14.8 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Somewhat: Follow-up 2	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Quite a bit: Follow-up 2	3.6 Percentage of Participants	4.0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Very much: Follow-up 2	0.9 Percentage of Participants	2.2 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Not at all: Follow-up 4	46.2 Percentage of Participants	37.7 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: A little bit: Follow-up 4	10.4 Percentage of Participants	12.1 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Somewhat: Follow-up 4	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Quite a bit: Follow-up 4	3.2 Percentage of Participants	4.5 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q1: Very much: Follow-up 4	1.4 Percentage of Participants	1.3 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Not at all: Baseline	64.7 Percentage of Participants	67.3 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: A little bit: Baseline	21.3 Percentage of Participants	17.9 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Somewhat: Baseline	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Quite a bit: Baseline	3.2 Percentage of Participants	5.8 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Very much: Baseline	0.5 Percentage of Participants	0.4 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Not at all: Neoadjuvant Cycle 3	14.0 Percentage of Participants	24.2 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: A little bit: Neoadjuvant Cycle 3	40.7 Percentage of Participants	38.6 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Somewhat: Neoadjuvant Cycle 3	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Quite a bit: Neoadjuvant Cycle 3	18.6 Percentage of Participants	14.8 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Very much: Neoadjuvant Cycle 3	6.8 Percentage of Participants	4.5 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Not at all: Neoadjuvant Cycle 5	21.3 Percentage of Participants	25.6 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: A little bit: Neoadjuvant Cycle 5	35.7 Percentage of Participants	37.7 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Somewhat: Neoadjuvant Cycle 5	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Quite a bit: Neoadjuvant Cycle 5	20.4 Percentage of Participants	12.6 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Very much: Neoadjuvant Cycle 5	5.0 Percentage of Participants	4.0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Not at all: Pre-Surgery	21.3 Percentage of Participants	27.4 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: A little bit: Pre-Surgery	33.9 Percentage of Participants	37.2 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Somewhat: Pre-Surgery	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Quite a bit: Pre-Surgery	15.4 Percentage of Participants	8.1 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Very much: Pre-Surgery	6.3 Percentage of Participants	4.0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Not at all: Adjuvant Cycle 4	23.5 Percentage of Participants	24.2 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: A little bit: Adjuvant Cycle 4	33.0 Percentage of Participants	30.9 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Somewhat: Adjuvant Cycle 4	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Quite a bit: Adjuvant Cycle 4	13.1 Percentage of Participants	9.4 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Very much: Adjuvant Cycle 4	9.0 Percentage of Participants	4.9 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Not at all: Adjuvant Cycle 8	23.1 Percentage of Participants	25.6 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: A little bit: Adjuvant Cycle 8	35.7 Percentage of Participants	24.2 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Somewhat: Adjuvant Cycle 8	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Quite a bit: Adjuvant Cycle 8	12.2 Percentage of Participants	9.9 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Very much: Adjuvant Cycle 8	5.0 Percentage of Participants	4.5 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Not at all: End of Therapy	27.1 Percentage of Participants	27.4 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: A little bit: End of Therapy	33.9 Percentage of Participants	30.0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Somewhat: End of Therapy	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Quite a bit: End of Therapy	10.0 Percentage of Participants	13.5 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Very much: End of Therapy	6.8 Percentage of Participants	3.1 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Not at all: Follow-up 2	36.2 Percentage of Participants	27.8 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: A little bit: Follow-up 2	25.8 Percentage of Participants	25.6 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Somewhat: Follow-up 2	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Quite a bit: Follow-up 2	4.1 Percentage of Participants	6.3 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Very much: Follow-up 2	1.8 Percentage of Participants	1.3 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Not at all: Follow-up 4	39.8 Percentage of Participants	30.0 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: A little bit: Follow-up 4	14.5 Percentage of Participants	18.8 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Quite a bit: Follow-up 4	4.5 Percentage of Participants	4.5 Percentage of Participants
Percentage of Participants by Response for Skin Problem Single Items Q2: Very much: Follow-up 4	2.7 Percentage of Participants	2.2 Percentage of Participants

SECONDARY outcome

Timeframe: From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period

Population: 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.

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.

Outcome measures

Outcome measures
Measure	TCH + P n=193 Participants 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).	T-DM1 + P n=205 Participants 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).
Percentage of Participants With a Clinically Meaningful Deterioration in Global Health Status (GHS)/Quality of Life (QoL) Score	69.9 Percentage of Participants	45.4 Percentage of Participants

SECONDARY outcome

Timeframe: From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period

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.

Outcome measures

Outcome measures
Measure	TCH + P n=191 Participants 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).	T-DM1 + P n=200 Participants 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).
Time to Clinically Meaningful Deterioration in GHS/QoL Score	3.02 months 95% Confidence Interval 2.83 • Interval 2.83 to 3.38	4.63 months 95% Confidence Interval 4.11 • Interval 4.11 to 7.98

SECONDARY outcome

Timeframe: From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period

Population: Patients of the ITT population with a baseline assessment and at least one post-treatment assessment was included in this analysis.

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.

Outcome measures

Outcome measures
Measure	TCH + P n=191 Participants 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).	T-DM1 + P n=200 Participants 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).
Time to Clinically Meaningful Deterioration in Function Subscale Physical Function	2.79 months Interval 2.79 to 2.96	4.86 months Interval 4.4 to 7.98
Time to Clinically Meaningful Deterioration in Function Subscale Role Function	2.79 months Interval 2.17 to 2.89	4.44 months Interval 4.04 to 4.53
Time to Clinically Meaningful Deterioration in Function Subscale Cognitive Function	3.42 months Interval 3.02 to 4.24	4.44 months Interval 4.21 to Upper limit not reached.

SECONDARY outcome

Timeframe: 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

Population: 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.

Only participants who received trastuzumab were to be analyzed for this outcome.

Outcome measures

Outcome measures
Measure	TCH + P n=214 Participants 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).	T-DM1 + P 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).
Maximum Observed Serum Concentration (Cmax) of Trastuzumab Cycle 1 (neoadjuvant period)	167 micrograms per milliliter (mcg/mL) Standard Deviation 47.1	—
Maximum Observed Serum Concentration (Cmax) of Trastuzumab Cycle 6 (neoadjuvant period)	148 micrograms per milliliter (mcg/mL) Standard Deviation 44.7	—
Maximum Observed Serum Concentration (Cmax) of Trastuzumab Cycle 1 (adjuvant period)	159 micrograms per milliliter (mcg/mL) Standard Deviation 36.2	—
Maximum Observed Serum Concentration (Cmax) of Trastuzumab Cycle 6 (adjuvant period)	181 micrograms per milliliter (mcg/mL) Standard Deviation 30.7	—

SECONDARY outcome

Timeframe: 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.

Only participants who received trastuzumab emtansine were to be analyzed for this outcome.

Outcome measures

Outcome measures
Measure	TCH + P n=222 Participants 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).	T-DM1 + P 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).
Cmax of Trastuzumab Emtansine and Total Trastuzumab Trastuzumab emtansine: C1 (neoadjuvant)	80.4 mcg/mL Standard Deviation 26.5	—
Cmax of Trastuzumab Emtansine and Total Trastuzumab Trastuzumab emtansine: C6 (neoadjuvant)	71.7 mcg/mL Standard Deviation 30.2	—
Cmax of Trastuzumab Emtansine and Total Trastuzumab Total Trastuzumab: C1 (neoadjuvant)	79.1 mcg/mL Standard Deviation 25.7	—
Cmax of Trastuzumab Emtansine and Total Trastuzumab Total Trastuzumab: C6 (neoadjuvant)	79.1 mcg/mL Standard Deviation 31.1	—
Cmax of Trastuzumab Emtansine and Total Trastuzumab Trastuzumab emtansine: C1 (adjuvant)	70.4 mcg/mL Standard Deviation 22.7	—
Cmax of Trastuzumab Emtansine and Total Trastuzumab Trastuzumab emtansine: C6 (adjuvant)	73.1 mcg/mL Standard Deviation 21.8	—
Cmax of Trastuzumab Emtansine and Total Trastuzumab Total Trastuzumab: C1 (adjuvant)	73.0 mcg/mL Standard Deviation 23.2	—
Cmax of Trastuzumab Emtansine and Total Trastuzumab Total Trastuzumab: C6 (adjuvant)	82.6 mcg/mL Standard Deviation 23.7	—

SECONDARY outcome

Timeframe: 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

Only participants who received trastuzumab were to be analyzed for this outcome.

Outcome measures

Outcome measures
Measure	TCH + P n=214 Participants 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).	T-DM1 + P 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).
Minimum Observed Serum Concentration (Cmin) of Trastuzumab Trastuzumab (neoadjuvant period)	45.8 mcg/mL Standard Deviation 17.8	—
Minimum Observed Serum Concentration (Cmin) of Trastuzumab Trastuzumab (adjuvant period)	21.8 mcg/mL Standard Deviation 0.153	—

SECONDARY outcome

Timeframe: 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

Only participants who received trastuzumab emtansine were to be analyzed for this outcome.

Outcome measures

Outcome measures
Measure	TCH + P n=222 Participants 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).	T-DM1 + P 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).
Cmin of Trastuzumab Emtansine and Total Trastuzumab Trastuzumab emtansine (neoadjuvant)	3.04 mcg/mL Standard Deviation 7.43	—
Cmin of Trastuzumab Emtansine and Total Trastuzumab Total Trastuzumab (neoadjuvant)	12.3 mcg/mL Standard Deviation 8.68	—
Cmin of Trastuzumab Emtansine and Total Trastuzumab Trastuzumab emtansine (adjuvant)	4.09 mcg/mL Standard Deviation 11.7	—
Cmin of Trastuzumab Emtansine and Total Trastuzumab Total Trastuzumab (adjuvant)	8.70 mcg/mL Standard Deviation 6.98	—

SECONDARY outcome

Timeframe: 15-30 min post-study treatment infusion (Cmax) on Day 1 of Cycle 1 and 6 in neoadjuvant and adjuvant period

DM1 is the metabolite of trastuzumab emtansine. Only participants who received trastuzumab emtansine were to be analyzed for this outcome.

Outcome measures

Outcome measures
Measure	TCH + P n=222 Participants 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).	T-DM1 + P 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).
Plasma N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) Concentrations C1: 15-30 min post-dose (neoadjuvant)	4.64 nanograms per milliliter (ng/mL) Standard Deviation 2.33	—
Plasma N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) Concentrations C6: 15-30 min post-dose (neoadjuvant)	4.73 nanograms per milliliter (ng/mL) Standard Deviation 2.61	—
Plasma N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) Concentrations C1: 15-30 min post-dose (adjuvant)	4.49 nanograms per milliliter (ng/mL) Standard Deviation 2.33	—
Plasma N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) Concentrations C6: 15-30 min post-dose (adjuvant)	5.15 nanograms per milliliter (ng/mL) Standard Deviation 8.28	—

SECONDARY outcome

Timeframe: 15-30 min post-study treatment infusion (Cmax) on Day 1 of Cycle 1 and 6 in neoadjuvant and adjuvant period

Outcome measures

Outcome measures
Measure	TCH + P n=222 Participants 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).	T-DM1 + P 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).
Serum Levels of Plasma DM1-Containing Catabolites Concentrations (in ng/mL) (Nonreducible Thioether Linker [MCC]-DM1 and Lysine [Lys]-MCC-DM1) C1: MCC-DM1 (Neoadjuvant Period)	8.18 ng/mL Standard Deviation 7.23	—
Serum Levels of Plasma DM1-Containing Catabolites Concentrations (in ng/mL) (Nonreducible Thioether Linker [MCC]-DM1 and Lysine [Lys]-MCC-DM1) C1: Lys-MCC-DM1 (Neoadjuvant period)	NA ng/mL Standard Deviation NA not reported since more than 1/3 of the results are LTR (Lower than reportable)	—
Serum Levels of Plasma DM1-Containing Catabolites Concentrations (in ng/mL) (Nonreducible Thioether Linker [MCC]-DM1 and Lysine [Lys]-MCC-DM1) C6: MCC-DM1 (Neoadjuvant Period)	8.22 ng/mL Standard Deviation 8.03	—
Serum Levels of Plasma DM1-Containing Catabolites Concentrations (in ng/mL) (Nonreducible Thioether Linker [MCC]-DM1 and Lysine [Lys]-MCC-DM1) C6: Lys-MCC-DM1 (Neoadjuvant period)	NA ng/mL Standard Deviation NA not reported since more than 1/3 of the results are LTR (Lower than reportable)	—
Serum Levels of Plasma DM1-Containing Catabolites Concentrations (in ng/mL) (Nonreducible Thioether Linker [MCC]-DM1 and Lysine [Lys]-MCC-DM1) C1: MCC-DM1 (Adjuvant Period)	7.98 ng/mL Standard Deviation 6.46	—
Serum Levels of Plasma DM1-Containing Catabolites Concentrations (in ng/mL) (Nonreducible Thioether Linker [MCC]-DM1 and Lysine [Lys]-MCC-DM1) C1: Lys-MCC-DM1 (Adjuvant period)	NA ng/mL Standard Deviation NA not reported since more than 1/3 of the results are LTR (Lower than reportable)	—
Serum Levels of Plasma DM1-Containing Catabolites Concentrations (in ng/mL) (Nonreducible Thioether Linker [MCC]-DM1 and Lysine [Lys]-MCC-DM1) C6: MCC-DM1 (Adjuvant Period)	7.90 ng/mL Standard Deviation 5.37	—
Serum Levels of Plasma DM1-Containing Catabolites Concentrations (in ng/mL) (Nonreducible Thioether Linker [MCC]-DM1 and Lysine [Lys]-MCC-DM1) C6: Lys-MCC-DM1 (Adjuvant period)	NA ng/mL Standard Deviation NA not reported since more than 1/3 of the results are LTR (Lower than reportable)	—

SECONDARY outcome

Timeframe: 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

Population: 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.

Outcome measures

Outcome measures
Measure	TCH + P n=210 Participants 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).	T-DM1 + P 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).
Percentage of Participants With ATA to Trastuzumab Neoadjuvant Phase (baseline)	11 Percentage of participants	—
Percentage of Participants With ATA to Trastuzumab Neoadjuvant Phase (post-baseline)	2.6 Percentage of participants	—
Percentage of Participants With ATA to Trastuzumab Adjuvant Phase (baseline)	5.4 Percentage of participants	—
Percentage of Participants With ATA to Trastuzumab Adjuvant Phase (post-baseline)	5.0 Percentage of participants	—

SECONDARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	TCH + P n=221 Participants 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).	T-DM1 + P n=223 Participants 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).
Percentage of Participants by Response for Hair Loss Single Item Not at all: Baseline	81.4 Percentage of Participants	87.4 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item A little bit: Baseline	7.7 Percentage of Participants	4.0 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Somewhat: Baseline	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Quite a bit: Baseline	0.5 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Very much: Baseline	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Not at all: Neoadjuvant Cycle 3	8.6 Percentage of Participants	65.0 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item A little bit: Neoadjuvant Cycle 3	11.3 Percentage of Participants	16.6 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Somewhat: Neoadjuvant Cycle 3	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Quite a bit: Neoadjuvant Cycle 3	20.8 Percentage of Participants	0.4 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Very much: Neoadjuvant Cycle 3	39.4 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Not at all: Neoadjuvant Cycle 5	20.4 Percentage of Participants	58.7 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item A little bit: Neoadjuvant Cycle 5	19.9 Percentage of Participants	19.3 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Somewhat: Neoadjuvant Cycle 5	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Quite a bit: Neoadjuvant Cycle 5	15.8 Percentage of Participants	1.3 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Very much: Neoadjuvant Cycle 5	26.2 Percentage of Participants	0.4 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Not at all: Pre-Surgery	30.8 Percentage of Participants	49.8 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item A little bit: Pre-Surgery	13.6 Percentage of Participants	24.7 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Somewhat: Pre-Surgery	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Quite a bit: Pre-Surgery	11.3 Percentage of Participants	2.2 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Very much: Pre-Surgery	21.3 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Not at all: Adjuvant Cycle 4	67.9 Percentage of Participants	50.2 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item A little bit: Adjuvant Cycle 4	5.0 Percentage of Participants	15.7 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Somewhat: Adjuvant Cycle 4	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Quite a bit: Adjuvant Cycle 4	3.2 Percentage of Participants	2.2 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Very much: Adjuvant Cycle 4	2.7 Percentage of Participants	1.3 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Not at all: Adjuvant Cycle 8	70.1 Percentage of Participants	48.9 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item A little bit: Adjuvant Cycle 8	4.1 Percentage of Participants	14.3 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Somewhat: Adjuvant Cycle 8	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Quite a bit: Adjuvant Cycle 8	0.9 Percentage of Participants	0.9 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Very much: Adjuvant Cycle 8	0.9 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Not at all: End of Therapy	69.7 Percentage of Participants	57.8 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item A little bit: End of Therapy	5.4 Percentage of Participants	14.8 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Somewhat: End of Therapy	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Quite a bit: End of Therapy	0.9 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Very much: End of Therapy	1.8 Percentage of Participants	1.3 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Not at all: Follow-up 2	55.7 Percentage of Participants	48.4 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item A little bit: Follow-up 2	9.0 Percentage of Participants	11.7 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Somewhat: Follow-up 2	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Quite a bit: Follow-up 2	1.4 Percentage of Participants	0.4 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Very much: Follow-up 2	1.8 Percentage of Participants	0.4 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Not at all: Follow-up 4	52.9 Percentage of Participants	41.3 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item A little bit: Follow-up 4	7.2 Percentage of Participants	11.2 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Somewhat: Follow-up 4	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Quite a bit: Follow-up 4	0 Percentage of Participants	2.7 Percentage of Participants
Percentage of Participants by Response for Hair Loss Single Item Very much: Follow-up 4	1.4 Percentage of Participants	0.4 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline to end of study (approximately 47 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	TCH + P n=219 Participants 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).	T-DM1 + P n=223 Participants 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).
Percentage of Participants With Selected Adverse Events (AEs) Hepatotoxicity	14.2 Percentage of Participants	39.0 Percentage of Participants
Percentage of Participants With Selected Adverse Events (AEs) Pulmonary Toxicity	0.9 Percentage of Participants	4.9 Percentage of Participants
Percentage of Participants With Selected Adverse Events (AEs) Cardiac Dysfunction	4.6 Percentage of Participants	1.3 Percentage of Participants
Percentage of Participants With Selected Adverse Events (AEs) Neutropenia	39.7 Percentage of Participants	8.1 Percentage of Participants
Percentage of Participants With Selected Adverse Events (AEs) Thrombocytopenia	22.8 Percentage of Participants	17.9 Percentage of Participants
Percentage of Participants With Selected Adverse Events (AEs) Peripheral Neuropathy	47.5 Percentage of Participants	28.7 Percentage of Participants
Percentage of Participants With Selected Adverse Events (AEs) Hemorrhage	19.2 Percentage of Participants	33.2 Percentage of Participants
Percentage of Participants With Selected Adverse Events (AEs) IRR/Hypersensitivity	13.7 Percentage of Participants	22.9 Percentage of Participants
Percentage of Participants With Selected Adverse Events (AEs) IRR/Hypersensitivity symptoms	7.8 Percentage of Participants	19.3 Percentage of Participants
Percentage of Participants With Selected Adverse Events (AEs) Rash	44.7 Percentage of Participants	36.8 Percentage of Participants
Percentage of Participants With Selected Adverse Events (AEs) Diarrhea	76.7 Percentage of Participants	38.6 Percentage of Participants
Percentage of Participants With Selected Adverse Events (AEs) Mucositis	43.8 Percentage of Participants	24.7 Percentage of Participants

SECONDARY outcome

Timeframe: From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period

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.

Outcome measures

Outcome measures
Measure	TCH + P n=193 Participants 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).	T-DM1 + P n=205 Participants 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).
Percentage of Participants With a Clinically Meaningful Deterioration in Function Subscales Cognitive Functioning	59.1 Percentage of Participants	42.4 Percentage of Participants
Percentage of Participants With a Clinically Meaningful Deterioration in Function Subscales Physical Functioning	72.5 Percentage of Participants	40.0 Percentage of Participants
Percentage of Participants With a Clinically Meaningful Deterioration in Function Subscales Role Functioning	76.7 Percentage of Participants	47.8 Percentage of Participants

SECONDARY outcome

Timeframe: 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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	TCH + P n=219 Participants 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).	T-DM1 + P 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).
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to TDM-1 Neoadjuvant Phase (Baseline)	5.5 Percentage of Participants	—
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to TDM-1 Neoadjuvant Phase (Post-Baseline)	7.5 Percentage of Participants	—
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to TDM-1 Adjuvant Phase (Baseline)	11.7 Percentage of Participants	—
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to TDM-1 Adjuvant Phase (Post-baseline)	13.1 Percentage of Participants	—

SECONDARY outcome

Timeframe: From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period

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.

Outcome measures

Outcome measures
Measure	TCH + P n=194 Participants 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).	T-DM1 + P n=205 Participants 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).
Percentage of Participants With a Clinically Meaningful Increase in Symptom Subscales Appetite Loss	61.1 Percentage of Participants	47.8 Percentage of Participants
Percentage of Participants With a Clinically Meaningful Increase in Symptom Subscales Any Hair Loss	91.2 Percentage of Participants	40.5 Percentage of Participants
Percentage of Participants With a Clinically Meaningful Increase in Symptom Subscales Systemic Therapy Side-Effects	89.7 Percentage of Participants	75.1 Percentage of Participants
Percentage of Participants With a Clinically Meaningful Increase in Symptom Subscales Constipation	33.2 Percentage of Participants	32.7 Percentage of Participants
Percentage of Participants With a Clinically Meaningful Increase in Symptom Subscales Diarrhea	79.3 Percentage of Participants	50.7 Percentage of Participants
Percentage of Participants With a Clinically Meaningful Increase in Symptom Subscales Dyspnea	56.0 Percentage of Participants	31.2 Percentage of Participants
Percentage of Participants With a Clinically Meaningful Increase in Symptom Subscales Fatigue	87.6 Percentage of Participants	68.8 Percentage of Participants
Percentage of Participants With a Clinically Meaningful Increase in Symptom Subscales Nausea/Vomiting	66.3 Percentage of Participants	43.9 Percentage of Participants
Percentage of Participants With a Clinically Meaningful Increase in Symptom Subscales Pain	56.0 Percentage of Participants	36.6 Percentage of Participants
Percentage of Participants With a Clinically Meaningful Increase in Symptom Subscales Insomnia	42.5 Percentage of Participants	30.2 Percentage of Participants

Adverse Events

TCH + P

Serious events: 70 serious events

Other events: 217 other events

Deaths: 5 deaths

T-DM1 + P

Serious events: 30 serious events

Other events: 212 other events

Deaths: 6 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER