Trial Outcomes & Findings for A Study of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy in Patients With HER2-Positive Breast Cancer Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Preoperative Therapy (KATHERINE) (NCT NCT01772472)

Last Updated: 2025-07-22

Results Overview

IDFS event was defined as the first occurrence of any one of the following events: ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site-other than the 2 above-mentioned sites - that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; death attributable to any cause including breast cancer, non-breast cancer or unknown cause . 3-year IDFS rate in ITT population was estimated using Kaplan Meier (KM) method and the percentage of participants who were event-free 3 years after randomization was estimated.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1486 participants

Primary outcome timeframe

At Year 3

Results posted on

2025-07-22

Participant Flow

A total of 1486 participants with human epidermal growth factor receptor 2 (HER2)-positive primary breast cancer who had residual invasive disease in either the breast or axillary lymph nodes took part in the study at 268 investigative sites across 28 countries from April 03, 2013 to May 23, 2024.

Participants received either trastuzumab or trastuzumab emtansine (T-DM1). 1 participant randomized to trastuzumab arm was untreated, later re-randomized to T-DM1 arm \& received treatment. Another participant in the trastuzumab arm received 13 cycles of trastuzumab \& 1 of T-DM1. Both these participants were included in the trastuzumab ITT population and T-DM1 safety analysis. 1 participant in T-DM1 arm received 9 cycles of trastuzumab \& included in trastuzumab safety analysis.

Participant milestones

Participant milestones
Measure	Trastuzumab Participants received trastuzumab, 6 milligram per kilograms (mg/kg), intravenously (IV), every 3 weeks (Q3W), as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Overall Study STARTED	743	743
Overall Study Safety-evaluable (SE) Population	720	740
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	743	743

Reasons for withdrawal

Reasons for withdrawal
Measure	Trastuzumab Participants received trastuzumab, 6 milligram per kilograms (mg/kg), intravenously (IV), every 3 weeks (Q3W), as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Overall Study Death	126	94
Overall Study Lost to Follow-up	51	50
Overall Study Other	9	7
Overall Study Physician Decision	1	7
Overall Study Withdrawal by Subject	115	90
Overall Study Follow-up Terminated by Sponsor	441	495

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Trastuzumab n=743 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=743 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Total n=1486 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	675 Participants n=5 Participants	685 Participants n=7 Participants	1360 Participants n=5 Participants
Age, Categorical >=65 years	68 Participants n=5 Participants	58 Participants n=7 Participants	126 Participants n=5 Participants
Sex: Female, Male Female	740 Participants n=5 Participants	741 Participants n=7 Participants	1481 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	107 Participants n=5 Participants	91 Participants n=7 Participants	198 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	543 Participants n=5 Participants	579 Participants n=7 Participants	1122 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	93 Participants n=5 Participants	73 Participants n=7 Participants	166 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	50 Participants n=5 Participants	36 Participants n=7 Participants	86 Participants n=5 Participants
Race (NIH/OMB) Asian	64 Participants n=5 Participants	65 Participants n=7 Participants	129 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	19 Participants n=5 Participants	21 Participants n=7 Participants	40 Participants n=5 Participants
Race (NIH/OMB) White	530 Participants n=5 Participants	551 Participants n=7 Participants	1081 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	77 Participants n=5 Participants	69 Participants n=7 Participants	146 Participants n=5 Participants

PRIMARY outcome

Timeframe: At Year 3

Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.

Outcome measures

Outcome measures
Measure	Trastuzumab n=743 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=743 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Invasive Disease-free Survival (IDFS) Rate at 3 Years	77.12 percentage of participants Interval 73.96 to 80.28	88.44 percentage of participants Interval 86.07 to 90.81

SECONDARY outcome

Timeframe: At Year 3

Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.

IDFS including SPNBC was defined the same way as IDFS but including second primary non breast invasive cancer as an event (with the exception of non-melanoma skin cancers and carcinoma in situ \[CIS\] of any site). IDFS event was defined as outlined in the description for IDFS rate outcome measure (OM) number 1. 3-year IDFS including SPNBC rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 3 years after randomization was estimated.

Outcome measures

Outcome measures
Measure	Trastuzumab n=743 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=743 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
IDFS Including Second Primary Non-breast Cancer (SPNBC) Rate at 3 Years	76.98 percentage of participants Interval 73.82 to 80.15	87.87 percentage of participants Interval 85.45 to 90.29

SECONDARY outcome

Timeframe: At Year 7

Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.

IDFS including SPNBC was defined the same way as IDFS but including second primary non breast invasive cancer as an event (with the exception of non-melanoma skin cancers and CIS of any site). IDFS event was defined as outlined in the description for IDFS rate OM number 1. 7-year IDFS including SPNBC rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 7 years after randomization was estimated.

Outcome measures

Outcome measures
Measure	Trastuzumab n=743 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=743 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
IDFS Including SPNBC Rate at 7 Years	66.19 percentage of participants Interval 62.59 to 69.8	79.81 percentage of participants Interval 76.79 to 82.82

SECONDARY outcome

Timeframe: At Year 8

Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.

IDFS including SPNBC was defined the same way as IDFS but including second primary non breast invasive cancer as an event (with the exception of non-melanoma skin cancers and CIS of any site). IDFS event was defined as outlined in the description for IDFS rate OM number 1. 8-year IDFS including SPNBC rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 8 years after randomization was estimated.

Outcome measures

Outcome measures
Measure	Trastuzumab n=743 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=743 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
IDFS Including SPNBC Rate at 8 Years	63.65 percentage of participants Interval 59.96 to 67.34	77.76 percentage of participants Interval 74.6 to 80.92

SECONDARY outcome

Timeframe: At Year 3

Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.

DFS was defined as the time between randomization and the date of the first occurrence of an IDFS event including SPNBC event or contralateral or ipsilateral ductal carcinoma in situ (DCIS). IDFS event was defined as outlined in the description for IDFS rate OM number 1. 3-year DFS rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 3 years after randomization was estimated.

Outcome measures

Outcome measures
Measure	Trastuzumab n=743 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=743 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Disease-free Survival (DFS) Rate at 3 Years	76.98 percentage of participants Interval 73.82 to 80.15	87.59 percentage of participants Interval 85.15 to 90.03

SECONDARY outcome

Timeframe: At Year 7

Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.

DFS was defined as the time between randomization and the date of the first occurrence of an IDFS event including SPNBC event or contralateral or ipsilateral DCIS. IDFS event was defined as outlined in the description for IDFS rate OM number 1. 7-year DFS rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 7 years after randomization was estimated.

Outcome measures

Outcome measures
Measure	Trastuzumab n=743 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=743 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
DFS Rate at 7 Years	66.03 percentage of participants Interval 62.42 to 69.64	79.37 percentage of participants Interval 76.33 to 82.42

SECONDARY outcome

Timeframe: At Year 8

Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.

DFS was defined as the time between randomization and the date of the first occurrence of an IDFS event including SPNBC event or contralateral or ipsilateral DCIS. IDFS event was defined as outlined in the description for IDFS rate OM number 1. 8-year DFS rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 8 years after randomization was estimated.

Outcome measures

Outcome measures
Measure	Trastuzumab n=743 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=743 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
DFS Rate at 8 Years	63.49 percentage of participants Interval 59.8 to 67.18	77.14 percentage of participants Interval 73.95 to 80.33

SECONDARY outcome

Timeframe: At Year 5

Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.

OS was defined as the time from randomization to death due to any cause. 5-year OS event-free rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 5 years after randomization was estimated.

Outcome measures

Outcome measures
Measure	Trastuzumab n=743 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=743 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Overall Survival (OS) Rate at 5 Years	87.71 percentage of participants Interval 85.2 to 90.22	91.40 percentage of participants Interval 89.3 to 93.5

SECONDARY outcome

Timeframe: At Year 7

Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.

OS was defined as the time from randomization to death due to any cause. 7-year OS event-free rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 7 years after randomization was estimated.

Outcome measures

Outcome measures
Measure	Trastuzumab n=743 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=743 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
OS Rate at 7 Years	84.38 percentage of participants Interval 81.59 to 87.17	89.07 percentage of participants Interval 86.72 to 91.43

SECONDARY outcome

Timeframe: At Year 8

Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.

OS was defined as the time from randomization to death due to any cause. 8-year OS event-free rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 8 years after randomization was estimated.

Outcome measures

Outcome measures
Measure	Trastuzumab n=743 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=743 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
OS Rate at 8 Years	81.91 percentage of participants Interval 78.94 to 84.89	87.16 percentage of participants Interval 84.62 to 89.7

SECONDARY outcome

Timeframe: At Year 3

Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.

DRFI was defined as the time between randomization and the date of distant breast cancer recurrence. 3-year DRFI event-free rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 3 years after randomization was estimated.

Outcome measures

Outcome measures
Measure	Trastuzumab n=743 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=743 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Distant Recurrence-free Interval (DRFI) Rate at 3 Years	83.26 percentage of participants Interval 80.43 to 86.08	89.95 percentage of participants Interval 87.72 to 92.19

SECONDARY outcome

Timeframe: At Year 7

Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.

DRFI was defined as the time between randomization and the date of distant breast cancer recurrence. 7-year DRFI event-free rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 7 years after randomization was estimated.

Outcome measures

Outcome measures
Measure	Trastuzumab n=743 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=743 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
DRFI Rate at 7 Years	76.22 percentage of participants Interval 72.95 to 79.48	84.55 percentage of participants Interval 81.82 to 87.27

SECONDARY outcome

Timeframe: At Year 8

Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.

DRFI was defined as the time between randomization and the date of distant breast cancer recurrence. 8-year DRFI event-free rate in the ITT population was estimated using KM method, and the percentage of participants who were event-free 8 years after randomization was estimated.

Outcome measures

Outcome measures
Measure	Trastuzumab n=743 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=743 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
DRFI Rate at 8 Years	74.28 percentage of participants Interval 70.9 to 77.65	83.82 percentage of participants Interval 81.03 to 86.62

SECONDARY outcome

Timeframe: From signing of informed consent till end of follow up (up to approximately 131 months)

Population: SE population included all randomized participants who received any amount of study treatment.

AE=any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. AE can therefore be any unfavorable \& unintended sign (including abnormal laboratory finding), symptom/disease temporally associated with use of a medicinal product, whether or not considered related to medicinal product. SAE=any AE that met any given criteria: fatal (i.e. AE causes/leads to death); life-threatening (i.e. AE, in view of investigator, placed the participant at immediate risk of death); required/prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity (i.e. AE results in substantial disruption of participant's ability to conduct normal life functions); congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study drug; significant medical event in investigator's judgment. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Trastuzumab n=720 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=740 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	93.3 percentage of participants	98.8 percentage of participants
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	8.1 percentage of participants	12.7 percentage of participants

SECONDARY outcome

Timeframe: Up to approximately 126 months

Population: SE population included all randomized participants who received any amount of study treatment.

Cardiac events were defined as death from cardiac cause or severe congestive heart failure (New York Heart Association \[NYHA\] Class III or IV) with a decrease in left ventricular ejection fraction (LVEF) of 10 percentage points or more from baseline to an LVEF of \< 50%. Other cardiac-related events (e.g., any symptomatic congestive heart failure \[CHF\] associated with a 10% drop in LVEF to \< 50%; asymptomatic declines in LVEF requiring dose delay) were summarized as adjudicated by the Cardiac Review Committee. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Trastuzumab n=720 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=740 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Percentage of Participants With Cardiac Events as Adjudicated by the Cardiac Review Committee	4.2 percentage of participants	3.1 percentage of participants

SECONDARY outcome

Timeframe: Up to approximately 64 months

Population: SE population included all randomized participants who received any amount of study treatment.

Hepatotoxicity events were summarized by treatment arm. Hepatotoxicity events were assessed using liver function laboratory test (LFT) results which included the analysis of baseline and post-baseline levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBILI), and alkaline phosphatase (ALK). Hepatic events, as adjudicated by the Hepatic Review Committee, are summarized. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Trastuzumab n=720 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=740 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Percentage of Participants With Hepatotoxicity Events as Adjudicated by the Hepatic Review Committee	0.1 percentage of participants	0.5 percentage of participants

SECONDARY outcome

Timeframe: Up to approximately 9.6 months

Population: SE population included all randomized participants who received any amount of study treatment.

Outcome measures

Outcome measures
Measure	Trastuzumab n=720 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=740 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Number of Participants Who Discontinued Treatment Due to AEs	15 Participants	134 Participants

SECONDARY outcome

Timeframe: From signing of informed consent till end of follow up (up to approximately 131 months)

Population: SE population included all randomized participants who received any amount of study treatment.

An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE was any AE that met any of the following criteria: fatal (i.e., the AE actually causes or leads to death); life-threatening (i.e., the AE, in the view of the investigator, placed the participant at immediate risk of death); required or prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity (i.e., the AE results in substantial disruption of the participant's ability to conduct normal life functions); congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study drug; significant medical event in the investigator's judgment.

Outcome measures

Outcome measures
Measure	Trastuzumab n=720 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=740 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Number of Participants With AEs and SAEs Leading to Death	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline, Cycles 5 &11, Follow-up (FU) Month 6, FU Month 12 (1 cycle = 21 days)

Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment. Overall number analyzed is the number of participants with data available for analysis. Number analyzed per timepoint are unique number of participants out of all the assessed participants with data available for analysis at the specified timepoint. Different participants may have contributed data for each timepoint.

The EORTC QLQ-C30 consists of 30 questions which assess five functional domains (physical, role, cognitive, emotional, and social), a global health status/quality of life (GHS/QoL) scale, three symptom scales (fatigue, pain, nausea, and vomiting), five single items (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea), and a perceived financial impact of the disease item. Most questions used a 4-point scale (1= Not at all to 4 = Very much; 2 questions used a 7-point scale \[1 = very poor to 7 = Excellent\]). Obtained scores are linearly transformed to a score range of 0-100, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms. A positive change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Trastuzumab n=743 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=743 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Baseline: Appetite Loss	7.9 score on a scale Standard Deviation 17.4	7.1 score on a scale Standard Deviation 16.4
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 5: Appetite Loss	1.0 score on a scale Standard Deviation 18.7	6.5 score on a scale Standard Deviation 23.7
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 11: Appetite Loss	-0.5 score on a scale Standard Deviation 17.2	2.9 score on a scale Standard Deviation 20.2
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 6: Appetite Loss	-1.6 score on a scale Standard Deviation 18.3	-1.7 score on a scale Standard Deviation 19.9
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 12: Appetite Loss	0.5 score on a scale Standard Deviation 20.3	-1.9 score on a scale Standard Deviation 20.1
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Baseline: Constipation	9.8 score on a scale Standard Deviation 20.2	9.5 score on a scale Standard Deviation 19.0
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 5: Constipation	1.0 score on a scale Standard Deviation 22.4	4.6 score on a scale Standard Deviation 22.6
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 11: Constipation	3.4 score on a scale Standard Deviation 23.6	7.3 score on a scale Standard Deviation 23.1
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 6: Constipation	4.1 score on a scale Standard Deviation 23.7	3.7 score on a scale Standard Deviation 23.3
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 12: Constipation	3.2 score on a scale Standard Deviation 23.2	4.3 score on a scale Standard Deviation 24.6
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Baseline: Diarrhea	8.8 score on a scale Standard Deviation 17.6	6.4 score on a scale Standard Deviation 14.9
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 5: Diarrhea	-1.6 score on a scale Standard Deviation 19.3	-1.5 score on a scale Standard Deviation 19.5
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 11: Diarrhea	-0.4 score on a scale Standard Deviation 21.4	-2.4 score on a scale Standard Deviation 17.5
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 6: Diarrhea	-3.4 score on a scale Standard Deviation 18.5	-1.9 score on a scale Standard Deviation 18.3
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 12: Diarrhea	-2.8 score on a scale Standard Deviation 18.9	-1.6 score on a scale Standard Deviation 18.4
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Baseline: Dyspnea	12.7 score on a scale Standard Deviation 20.7	11.0 score on a scale Standard Deviation 18.8
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 5: Dyspnea	2.3 score on a scale Standard Deviation 21.9	4.1 score on a scale Standard Deviation 22.4
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 11: Dyspnea	2.8 score on a scale Standard Deviation 21.2	2.7 score on a scale Standard Deviation 20.4
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 6: Dyspnea	3.3 score on a scale Standard Deviation 22.8	3.8 score on a scale Standard Deviation 22.7
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 12: Dyspnea	3.9 score on a scale Standard Deviation 24.9	5.3 score on a scale Standard Deviation 22.4
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Baseline: Fatigue	29.2 score on a scale Standard Deviation 21.1	28.0 score on a scale Standard Deviation 20.0
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 5: Fatigue	1.1 score on a scale Standard Deviation 20.1	5.5 score on a scale Standard Deviation 19.7
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 11: Fatigue	1.1 score on a scale Standard Deviation 20.5	3.8 score on a scale Standard Deviation 21.3
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 6: Fatigue	-1.4 score on a scale Standard Deviation 21.9	-0.1 score on a scale Standard Deviation 22.2
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 12: Fatigue	-0.1 score on a scale Standard Deviation 23.3	-0.1 score on a scale Standard Deviation 22.1
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Baseline: Financial Difficulties	28.6 score on a scale Standard Deviation 33.3	27.6 score on a scale Standard Deviation 31.9
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 5: Financial Difficulties	-3.1 score on a scale Standard Deviation 26.5	-3.0 score on a scale Standard Deviation 28.0
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 11: Financial Difficulties	-5.1 score on a scale Standard Deviation 27.6	-1.7 score on a scale Standard Deviation 28.7
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 6: Financial Difficulties	-8.4 score on a scale Standard Deviation 28.3	-6.5 score on a scale Standard Deviation 30.6
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 12: Financial Difficulties	-10.9 score on a scale Standard Deviation 30.5	-7.3 score on a scale Standard Deviation 31.0
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Baseline: Insomnia	30.6 score on a scale Standard Deviation 30.8	30.6 score on a scale Standard Deviation 29.2
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 5: Insomnia	1.9 score on a scale Standard Deviation 28.4	1.3 score on a scale Standard Deviation 29.7
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 11: Insomnia	2.4 score on a scale Standard Deviation 29.9	1.5 score on a scale Standard Deviation 30.3
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 6: Insomnia	1.8 score on a scale Standard Deviation 31.3	-0.9 score on a scale Standard Deviation 32.1
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 12: Insomnia	0.3 score on a scale Standard Deviation 30.4	0.7 score on a scale Standard Deviation 31.7
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Baseline: Nausea/Vomiting	3.3 score on a scale Standard Deviation 9.0	2.8 score on a scale Standard Deviation 8.0
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 5: Nausea/Vomiting	1.5 score on a scale Standard Deviation 11.2	3.2 score on a scale Standard Deviation 12.5
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 11: Nausea/Vomiting	1.3 score on a scale Standard Deviation 12.8	3.0 score on a scale Standard Deviation 11.8
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 6: Nausea/Vomiting	0.8 score on a scale Standard Deviation 10.4	0.2 score on a scale Standard Deviation 11.1
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 12: Nausea/Vomiting	0.4 score on a scale Standard Deviation 10.5	1.2 score on a scale Standard Deviation 10.9
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Baseline: Pain	22.2 score on a scale Standard Deviation 22.2	22.6 score on a scale Standard Deviation 22.8
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 5: Pain	0.0 score on a scale Standard Deviation 23.2	1.8 score on a scale Standard Deviation 23.9
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 11: Pain	0.1 score on a scale Standard Deviation 23.1	2.1 score on a scale Standard Deviation 24.4
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 6: Pain	-0.3 score on a scale Standard Deviation 24.6	-0.5 score on a scale Standard Deviation 24.3
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 12: Pain	-1.2 score on a scale Standard Deviation 25.6	-0.8 score on a scale Standard Deviation 25.4
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Baseline: Cognitive Functioning	83.3 score on a scale Standard Deviation 20.2	84.4 score on a scale Standard Deviation 19.0
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 5: Cognitive Functioning	-3.8 score on a scale Standard Deviation 18.4	-4.5 score on a scale Standard Deviation 18.7
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 11: Cognitive Functioning	-5.4 score on a scale Standard Deviation 21.3	-5.3 score on a scale Standard Deviation 19.6
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 6: Cognitive Functioning	-4.1 score on a scale Standard Deviation 22.0	-6.1 score on a scale Standard Deviation 21.6
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 12: Cognitive Functioning	-4.9 score on a scale Standard Deviation 22.2	-6.9 score on a scale Standard Deviation 21.7
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Baseline: Emotional Functioning	75.0 score on a scale Standard Deviation 22.0	75.2 score on a scale Standard Deviation 21.2
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 5: Emotional Functioning	-0.4 score on a scale Standard Deviation 20.0	-1.3 score on a scale Standard Deviation 21.3
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 11: Emotional Functioning	-1.0 score on a scale Standard Deviation 21.3	0.1 score on a scale Standard Deviation 22.0
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 6: Emotional Functioning	-2.9 score on a scale Standard Deviation 22.0	-0.8 score on a scale Standard Deviation 23.3
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 12: Emotional Functioning	-2.0 score on a scale Standard Deviation 22.7	-1.6 score on a scale Standard Deviation 23.5
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Baseline: Physical Functioning	84.5 score on a scale Standard Deviation 15.3	85.8 score on a scale Standard Deviation 14.1
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 5: Physical Functioning	0.3 score on a scale Standard Deviation 12.9	-1.6 score on a scale Standard Deviation 12.7
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 11: Physical Functioning	1.9 score on a scale Standard Deviation 14.2	-0.6 score on a scale Standard Deviation 14.6
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 6: Physical Functioning	2.8 score on a scale Standard Deviation 15.4	0.7 score on a scale Standard Deviation 15.1
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 12: Physical Functioning	2.7 score on a scale Standard Deviation 14.5	0.8 score on a scale Standard Deviation 14.5
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Baseline: Role Functioning	77.5 score on a scale Standard Deviation 25.0	78.6 score on a scale Standard Deviation 23.3
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 5: Role Functioning	2.0 score on a scale Standard Deviation 24.3	-0.2 score on a scale Standard Deviation 24.1
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 11: Role Functioning	4.0 score on a scale Standard Deviation 24.3	0.6 score on a scale Standard Deviation 24.5
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 6: Role Functioning	7.4 score on a scale Standard Deviation 25.8	3.6 score on a scale Standard Deviation 26.7
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 12: Role Functioning	8.0 score on a scale Standard Deviation 27.5	4.6 score on a scale Standard Deviation 25.5
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Baseline: Social Functioning	77.1 score on a scale Standard Deviation 24.1	76.8 score on a scale Standard Deviation 23.2
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 5: Social Functioning	4.0 score on a scale Standard Deviation 22.5	1.6 score on a scale Standard Deviation 23.8
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 11: Social Functioning	5.8 score on a scale Standard Deviation 24.0	2.5 score on a scale Standard Deviation 23.6
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 6: Social Functioning	8.5 score on a scale Standard Deviation 23.7	6.5 score on a scale Standard Deviation 26.1
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 12: Social Functioning	9.5 score on a scale Standard Deviation 25.1	7.4 score on a scale Standard Deviation 26.4
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Baseline: Global Health Status	71.2 score on a scale Standard Deviation 19.3	71.4 score on a scale Standard Deviation 18.0
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 5: Global Health Status	0.6 score on a scale Standard Deviation 18.9	-1.9 score on a scale Standard Deviation 19.6
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at Cycle 11: Global Health Status	1.7 score on a scale Standard Deviation 17.8	-0.5 score on a scale Standard Deviation 19.9
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 6: Global Health Status	2.5 score on a scale Standard Deviation 19.3	2.0 score on a scale Standard Deviation 19.2
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Change at FU Month 12: Global Health Status	3.2 score on a scale Standard Deviation 19.5	2.8 score on a scale Standard Deviation 20.1

SECONDARY outcome

Timeframe: Baseline, Cycles 5 &11, Follow-up (FU) Month 6, FU Month 12 (1 cycle = 21 days)

EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective \[FP\]) and four symptom scales (systemic side effects \[SE\], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Obtained scores are linearly transformed to a score range of 0-100. High score for functional scale indicated high/better level of functioning/healthy functioning. Higher scores for symptom scales represent higher levels of symptoms/problems. For functional scales, positive change from baseline indicated deterioration in QOL and negative change from baseline indicated an improvement in QOL. For symptom scales, positive change from baseline indicated an improvement in QOL and negative change from baseline indicated a deterioration in QOL.

Outcome measures

Outcome measures
Measure	Trastuzumab n=743 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=743 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at Cycle 5: Arm Symptoms	-2.8 score on a scale Standard Deviation 20.9	-2.6 score on a scale Standard Deviation 23.0
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Baseline: Body Image	69.8 score on a scale Standard Deviation 28.5	67.5 score on a scale Standard Deviation 28.5
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at Cycle 5: Body Image	1.5 score on a scale Standard Deviation 20.5	4.6 score on a scale Standard Deviation 22.7
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at Cycle 11: Body Image	3.4 score on a scale Standard Deviation 24.4	5.7 score on a scale Standard Deviation 23.9
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at FU Month 6: Body Image	3.6 score on a scale Standard Deviation 25.1	7.8 score on a scale Standard Deviation 25.8
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at FU Month 12: Body Image	6.2 score on a scale Standard Deviation 27.1	6.1 score on a scale Standard Deviation 27.2
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Baseline: FP	51.3 score on a scale Standard Deviation 31.2	50.1 score on a scale Standard Deviation 31.7
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at Cycle 5: FP	2.6 score on a scale Standard Deviation 28.3	6.5 score on a scale Standard Deviation 29.9
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at Cycle 11: FP	6.3 score on a scale Standard Deviation 30.0	6.1 score on a scale Standard Deviation 31.4
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at FU Month 6: FP	7.7 score on a scale Standard Deviation 33.5	8.1 score on a scale Standard Deviation 34.6
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at FU Month 12: FP	8.1 score on a scale Standard Deviation 31.1	8.2 score on a scale Standard Deviation 33.0
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Baseline: Sexual Enjoyment	50.9 score on a scale Standard Deviation 28.8	52.3 score on a scale Standard Deviation 28.5
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at Cycle 5: Sexual Enjoyment	2.3 score on a scale Standard Deviation 26.4	-1.9 score on a scale Standard Deviation 24.6
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at Cycle 11: Sexual Enjoyment	4.4 score on a scale Standard Deviation 27.5	4.4 score on a scale Standard Deviation 24.5
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at FU Month 6: Sexual Enjoyment	3.2 score on a scale Standard Deviation 28.1	0.3 score on a scale Standard Deviation 27.5
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at FU Month 12: Sexual Enjoyment	5.6 score on a scale Standard Deviation 26.0	1.8 score on a scale Standard Deviation 26.2
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Baseline: Sexual Function	20.2 score on a scale Standard Deviation 23.6	22.0 score on a scale Standard Deviation 23.4
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at Cycle 5: Sexual Function	3.3 score on a scale Standard Deviation 20.0	2.3 score on a scale Standard Deviation 20.0
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at Cycle 11: Sexual Function	3.1 score on a scale Standard Deviation 20.8	1.9 score on a scale Standard Deviation 20.3
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at FU Month 6: Sexual Function	5.1 score on a scale Standard Deviation 23.9	4.3 score on a scale Standard Deviation 23.1
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at FU Month 12: Sexual Function	5.9 score on a scale Standard Deviation 23.7	5.2 score on a scale Standard Deviation 22.7
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Baseline: Arm Symptoms	24.6 score on a scale Standard Deviation 21.1	24.5 score on a scale Standard Deviation 21.0
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at Cycle 11: Arm Symptoms	-2.6 score on a scale Standard Deviation 21.2	0.2 score on a scale Standard Deviation 24.2
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at FU Month 6: Arm Symptoms	-3.0 score on a scale Standard Deviation 23.5	-1.3 score on a scale Standard Deviation 24.2
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at FU Month 12: Arm Symptoms	-5.7 score on a scale Standard Deviation 22.8	-1.5 score on a scale Standard Deviation 22.6
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Baseline: Breast Symptoms	22.7 score on a scale Standard Deviation 19.1	21.4 score on a scale Standard Deviation 17.9
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at Cycle 5: Breast Symptoms	-1.1 score on a scale Standard Deviation 20.3	-1.1 score on a scale Standard Deviation 19.1
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at Cycle 11: Breast Symptoms	-3.7 score on a scale Standard Deviation 19.8	-0.6 score on a scale Standard Deviation 19.5
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at FU Month 6: Breast Function	-6.5 score on a scale Standard Deviation 20.0	-2.2 score on a scale Standard Deviation 19.7
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at Follow-up Month 12: Breast Function	-8.3 score on a scale Standard Deviation 19.9	-3.8 score on a scale Standard Deviation 19.2
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Baseline: Systemic Therapy Side Effects (SE)	16.7 score on a scale Standard Deviation 13.7	16.9 score on a scale Standard Deviation 14.1
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at Cycle 5: Systemic Therapy SE	0.7 score on a scale Standard Deviation 13.0	5.5 score on a scale Standard Deviation 15.3
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at Cycle 11: Systemic Therapy SE	1.2 score on a scale Standard Deviation 12.2	4.2 score on a scale Standard Deviation 15.4
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at FU Month 6: Systemic Therapy SE	1.9 score on a scale Standard Deviation 13.9	1.1 score on a scale Standard Deviation 15.3
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at FU Month 12: Systemic Therapy SE	1.3 score on a scale Standard Deviation 13.9	1.4 score on a scale Standard Deviation 16.3
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Baseline: Upset by Hair Loss Item	40.3 score on a scale Standard Deviation 35.6	50.7 score on a scale Standard Deviation 38.4
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at Cycle 5: Upset by Hair Loss Item	-5.1 score on a scale Standard Deviation 38.1	-17.6 score on a scale Standard Deviation 39.3
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at Cycle 11: Upset by Hair Loss Item	-28.6 score on a scale Standard Deviation 45.0	-14.3 score on a scale Standard Deviation 33.9
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at FU Month 6: Upset by Hair Loss Item	-12.0 score on a scale Standard Deviation 47.0	-15.2 score on a scale Standard Deviation 42.1
Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23) Change at FU Month 12: Upset by Hair Loss Item	-2.9 score on a scale Standard Deviation 37.5	-14.3 score on a scale Standard Deviation 41.6

SECONDARY outcome

Timeframe: Pre-infusion on Cycles 1, 2, 4 and 5; 15-30 minutes and 2 hours post-infusion on Cycles 1 and 4; treatment discontinuation/completion visit (up to approximately 64 months) (1 cycle = 21 days)

Population: Pharmacokinetic (PK)-evaluable population included all participants who received at least 1 dose of trastuzumab emtansine and had at least one evaluable post dose PK sample. Overall number analyzed is the number of participants with data available for analysis. Number analyzed per timepoint are unique number of participants out of all the assessed participants with data available for analysis at the specified timepoint. Different participants may have contributed data for each timepoint.

Outcome measures

Outcome measures
Measure	Trastuzumab n=423 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Serum Concentrations of Trastuzumab Emtansine Pre-infusion on Cycle 1	NA micrograms per milliliter (ug/mL) Geometric Coefficient of Variation NA The geometric mean and geometric coefficient of variation were not estimable as the samples were below the limit of quantification. The samples were taken prior to administration of the first dose.	—
Serum Concentrations of Trastuzumab Emtansine 15-30 minutes post-infusion on Cycle 1	63.0 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 101.8	—
Serum Concentrations of Trastuzumab Emtansine 2 hours post-infusion on Cycle 1	67.4 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 60.0	—
Serum Concentrations of Trastuzumab Emtansine Pre-infusion on Cycle 2	1.69 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 110.7	—
Serum Concentrations of Trastuzumab Emtansine Pre-infusion on Cycle 4	1.73 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 95.7	—
Serum Concentrations of Trastuzumab Emtansine 15-30 minutes post-infusion on Cycle 4	68.5 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 59.4	—
Serum Concentrations of Trastuzumab Emtansine 2 hours post-infusion on Cycle 4	66.4 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 71.0	—
Serum Concentrations of Trastuzumab Emtansine Pre-infusion on Cycle 5	1.67 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 99.3	—
Serum Concentrations of Trastuzumab Emtansine Treatment Completion/Discontinuation	0.323 micrograms per milliliter (ug/mL) Geometric Coefficient of Variation 265.3	—

SECONDARY outcome

Timeframe: Pre-infusion, 15-30 minutes and 2 hour post-infusion on Cycles 1 and 4 (1 cycle = 21 days)

Population: PK-evaluable population included all participants who received atleast 1 dose of trastuzumab emtansine and had at least one evaluable post dose PK sample. Overall number analyzed is the number of participants with data available for analysis. Number analyzed per timepoint are unique number of participants out of all the assessed participants with data available for analysis at the specified timepoint. Different participants may have contributed data for each timepoint.

Concentration of DM1 in plasma was measured through the samples obtained from participants randomized to the trastuzumab emtansine arm. DM1 is an ant-microtubule agent derived from maytansine. In transtuzumab entansine, DM1 is linked to the antibody transtuzumab thus helping the drug to specifically target the HER 2- positive cancer cells.

Outcome measures

Outcome measures
Measure	Trastuzumab n=417 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Plasma Concentrations of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1) Pre-infusion on Cycle 1	NA nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA The geometric mean and geometric coefficient of variation were not estimable as majority of the values were lower than reportable.	—
Plasma Concentrations of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1) 15-30 minutes post-infusion on Cycle 1	4.21 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 57.4	—
Plasma Concentrations of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1) 2 hours post-infusion on Cycle 1	3.44 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 38.2	—
Plasma Concentrations of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1) Pre-infusion on Cycle 4	0.372 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation NA The geometric coefficient of variation was not estimable as majority of the values were lower than reportable or zero.	—
Plasma Concentrations of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1) 15-30 minutes post-infusion on Cycle 4	4.81 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 48.8	—
Plasma Concentrations of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1) 2 hours post-infusion on Cycle 4	3.70 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 41.0	—

SECONDARY outcome

Timeframe: Pre-infusion and 15-30 minutes post-infusion on Cycles 1 and 4; Treatment completion/discontinuation visit (up to approximately 64 months) (1 cycle = 21 days)

Population: PK-evaluable population included all participants who received at least 1 dose of trastuzumab and had at least one evaluable post dose PK sample. Overall number analyzed is the number of participants with data available for analysis. Number analyzed per timepoint are unique number of participants out of all the assessed participants with data available for analysis at the specified timepoint. Different participants may have contributed data for each timepoint.

Outcome measures

Outcome measures
Measure	Trastuzumab n=404 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Serum Concentrations of Trastuzumab Pre-infusion on Cycle 1	NA ug/mL Geometric Coefficient of Variation NA The geometric mean and geometric coefficient of variation were not estimable as the samples were below the limit of quantification. The samples were taken prior to administration of the first dose.	—
Serum Concentrations of Trastuzumab 15-30 minutes post-infusion on Cycle 1	208 ug/mL Geometric Coefficient of Variation 43.1	—
Serum Concentrations of Trastuzumab Pre-infusion on Cycle 4	64.8 ug/mL Geometric Coefficient of Variation 60.6	—
Serum Concentrations of Trastuzumab 15-30 minutes post-infusion on Cycle 4	218 ug/mL Geometric Coefficient of Variation 47.2	—
Serum Concentrations of Trastuzumab Treatment Completion/Discontinuation	58.7 ug/mL Geometric Coefficient of Variation 86.3	—

SECONDARY outcome

Timeframe: Pre-infusion on Day 1 of Cycles 1, 2, 4, and 5; 15-30 minutes and 2 hours post-infusion on Day 1 of Cycles 1 and 4 (1 cycle = 21 days)

Total trastuzumab is the sum of conjugated and unconjugated trastuzumab. Blood and serum samples were obtained from participants randomized to the trastuzumab arm.

Outcome measures

Outcome measures
Measure	Trastuzumab n=421 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Serum Concentrations of Total Trastuzumab Pre-infusion on Cycle 1	NA ug/mL Geometric Coefficient of Variation NA The geometric mean and geometric coefficient of variation were not estimable as the samples were below the limit of quantification. The samples were taken prior to administration of the first dose.	—
Serum Concentrations of Total Trastuzumab 15-30 minutes post-infusion on Cycle 1	71.8 ug/mL Geometric Coefficient of Variation 154.7	—
Serum Concentrations of Total Trastuzumab 2 hours post-infusion on Cycle 1	81.4 ug/mL Geometric Coefficient of Variation 74.3	—
Serum Concentrations of Total Trastuzumab Pre-infusion on Cycle 2	7.93 ug/mL Geometric Coefficient of Variation 256.8	—
Serum Concentrations of Total Trastuzumab Pre-infusion on Cycle 4	13.7 ug/mL Geometric Coefficient of Variation 78.0	—
Serum Concentrations of Total Trastuzumab 15-30 minutes post-infusion on Cycle 4	76.9 ug/mL Geometric Coefficient of Variation 46.5	—
Serum Concentrations of Total Trastuzumab 2 hours post-infusion on Cycle 4	81.5 ug/mL Geometric Coefficient of Variation 34.0	—
Serum Concentrations of Total Trastuzumab Pre-infusion on Cycle 5	8.90 ug/mL Geometric Coefficient of Variation 125.0	—

SECONDARY outcome

Timeframe: Up to 12 months

Population: SE population included all randomized participants who received any amount of study treatment.

Treatment duration was defined as the time between the first and the last infusion of trastuzumab emtansine.

Outcome measures

Outcome measures
Measure	Trastuzumab n=740 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Median Duration of Trastuzumab Emtansine Exposure	10 months Interval 1.0 to 12.0	—

SECONDARY outcome

Timeframe: Baseline (Day1 of Cycle1) and Post Baseline (Day 1 of Cycle 4 up to 3-4 months after last dose of the drug [up to approximately 13.6 months])

Population: SE Population included all randomized participants who received any amount of study treatment. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

ADA-positive participants after drug administration were determined for participants exposed to trastuzumab emtansine. For determining post-baseline incidence, participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the baseline titer result. The total number of participants who developed ADAs to trastuzumab emtansine was determined by summing the ADA-positive participants across all timepoints.

Outcome measures

Outcome measures
Measure	Trastuzumab n=740 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Number of Participants With Positive Anti-drug Antibodies (ADAs) to Trastuzumab Emtansine Baseline	17 Participants	—
Number of Participants With Positive Anti-drug Antibodies (ADAs) to Trastuzumab Emtansine Post-baseline	16 Participants	—

SECONDARY outcome

Timeframe: Baseline (Day1 of Cycle1) and Post Baseline (Day 1 of Cycle 4 up to 3-4 months after last dose of the drug [up to approximately 13.6 months])

ADA-positive participants after drug administration were determined for participants exposed to trastuzumab. For determining post-baseline incidence, participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 t.u. greater than the baseline titer result. The total number of participants who developed ADAs to trastuzumab was determined by summing the ADA-positive participants across all timepoints.

Outcome measures

Outcome measures
Measure	Trastuzumab n=720 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
Number of Participants With Positive ADAs to Trastuzumab Baseline	11 Participants	—
Number of Participants With Positive ADAs to Trastuzumab Post-baseline	15 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: At Year 7

Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.

IDFS event was defined as the first occurrence of any one of the following events: ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site-other than the 2 above-mentioned sites - that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; death attributable to any cause including breast cancer, non-breast cancer or unknown cause . 7-year IDFS rate in ITT population was estimated using KM method and the percentage of participants who were event-free 7 years after randomization was estimated.

Outcome measures

Outcome measures
Measure	Trastuzumab n=743 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=743 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
IDFS Rate at 7 Years	67.11 percentage of participants Interval 63.53 to 70.68	80.82 percentage of participants Interval 77.86 to 83.78

OTHER_PRE_SPECIFIED outcome

Timeframe: At Year 8

Population: ITT population included all participants who were randomized to the study regardless of whether they received any study treatment.

IDFS event was defined as the first occurrence of any one of the following events: ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site-other than the 2 above-mentioned sites - that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; death attributable to any cause including breast cancer, non-breast cancer or unknown cause . 8-year IDFS rate in ITT population was estimated using KM method and the percentage of participants who were event-free 8 years after randomization was estimated.

Outcome measures

Outcome measures
Measure	Trastuzumab n=743 Participants Participants received trastuzumab, 6 mg/kg, IV, Q3W, as a maintenance dose for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.	Trastuzumab Emtansine n=743 Participants Participants received trastuzumab emtansine, 3.6 mg/kg, IV, Q3W for 14 cycles (1 cycle = 21 days) or until disease recurrence or unacceptable toxicity which ever occurs first.
IDFS Rate at 8 Years	64.57 percentage of participants Interval 60.9 to 68.23	79.11 percentage of participants Interval 76.03 to 82.19

Adverse Events

Trastuzumab

Serious events: 58 serious events

Other events: 633 other events

Deaths: 126 deaths

Trastuzumab Emtansine

Serious events: 94 serious events

Other events: 719 other events

Deaths: 94 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