Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine Versus the Combination of Trastuzumab Plus Docetaxel in Patients With HER2-positive Breast Cancer (NCT NCT02144012)

Last Updated: 2017-03-07

Results Overview

PFS was defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments. Progression was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeter (mm) or the appearance of one or more new lesions.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

49 participants

Primary outcome timeframe

At time of clinical data cut-off (up to 20 months)

Results posted on

2017-03-07

Participant Flow

Only 49 participants of the originally planned 561 participants were enrolled in the study at the time of study termination.

Participant milestones

Participant milestones
Measure	Arm A: Trastuzumab Emtansine Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.	Arm B: Trastuzumab + Docetaxel Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W. Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.
Overall Study STARTED	34	15
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	34	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: Trastuzumab Emtansine Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.	Arm B: Trastuzumab + Docetaxel Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W. Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.
Overall Study Adverse Event	1	0
Overall Study Death	1	0
Overall Study Withdrawal by Subject	11	3
Overall Study Study Terminated by Sponsor	18	12
Overall Study Other	3	0

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine Versus the Combination of Trastuzumab Plus Docetaxel in Patients With HER2-positive Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Trastuzumab Emtansine n=34 Participants Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.	Arm B: Trastuzumab + Docetaxel n=15 Participants Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W. Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.	Total n=49 Participants Total of all reporting groups
Age, Continuous	53.7 years STANDARD_DEVIATION 9.5 • n=5 Participants	51.7 years STANDARD_DEVIATION 11.1 • n=7 Participants	53.1 years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	15 Participants n=7 Participants	49 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: At time of clinical data cut-off (up to 20 months)

Population: The intent-to-treat (ITT) population included all randomized participants grouped according to the treatment assigned at randomization.

Outcome measures

Outcome measures
Measure	Arm A: Trastuzumab Emtansine n=34 Participants Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.	Arm B: Trastuzumab + Docetaxel n=15 Participants Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W. Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.
Progression-Free Survival (PFS)	10.3 months Interval 4.2 to Not Available (NA) = parameter not estimable due to small number of participants included in analysis	8.2 months Interval 6.0 to 13.8

PRIMARY outcome

Timeframe: At time of clinical data cut-off (up to 20 months)

Population: The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Outcome measures

Outcome measures
Measure	Arm A: Trastuzumab Emtansine n=34 Participants Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.	Arm B: Trastuzumab + Docetaxel n=15 Participants Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W. Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.
Safety: Percentage of Participants With Adverse Events (AEs)	94.1 percentage of participants	100 percentage of participants

PRIMARY outcome

Timeframe: At time of clinical data cut-off (up to 20 months)

Population: The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.

Grade 3 and 4 AEs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0. Grade 3 was defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living, including bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. Grade 4 was defined as life-threatening consequences; urgent intervention indicated.

Outcome measures

Outcome measures
Measure	Arm A: Trastuzumab Emtansine n=34 Participants Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.	Arm B: Trastuzumab + Docetaxel n=15 Participants Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W. Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.
Safety: Percentage of Participants With Grade 3 and 4 AEs	20.6 percentage of participants	66.7 percentage of participants

PRIMARY outcome

Timeframe: At time of clinical data cut-off (up to 20 months)

Population: The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.

Outcome measures

Outcome measures
Measure	Arm A: Trastuzumab Emtansine n=34 Participants Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.	Arm B: Trastuzumab + Docetaxel n=15 Participants Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W. Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.
Percentage of Participants With Adverse Events Leading to Treatment Discontinuation	14.7 percentage of participants	20.0 percentage of participants

PRIMARY outcome

Timeframe: At time of clinical data cut-off (up to 20 months)

Population: The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.

Outcome measures

Outcome measures
Measure	Arm A: Trastuzumab Emtansine n=34 Participants Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.	Arm B: Trastuzumab + Docetaxel n=15 Participants Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W. Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.
Safety: Percentage of Participants With Adverse Events Leading to Treatment Interruption	11.8 percentage of participants	33.3 percentage of participants

PRIMARY outcome

Timeframe: At time of clinical data cut-off (up to 20 months)

Population: The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.

Outcome measures

Outcome measures
Measure	Arm A: Trastuzumab Emtansine n=34 Participants Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.	Arm B: Trastuzumab + Docetaxel n=15 Participants Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W. Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.
Safety: Percentage of Participants With Adverse Events Leading to Dose Reduction	2.9 percentage of participants	26.7 percentage of participants

PRIMARY outcome

Timeframe: At time of clinical data cut-off (up to 20 months)

Population: The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.

Significant decline in LVEF was defined as LVEF below 50% and decrease from baseline of 15% points or more. Echocardiogram or multiple-gated acquisition (MUGA) scan was used to assess LVEF.

Outcome measures

Outcome measures
Measure	Arm A: Trastuzumab Emtansine n=34 Participants Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.	Arm B: Trastuzumab + Docetaxel n=15 Participants Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W. Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.
Safety: Percentage of Participants With Significant Decline in Left Ventricular Ejection Fraction (LVEF)	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: At time of clinical data cut-off (up to 20 months)

Population: The ITT population included all randomized participants grouped according to the treatment assigned at randomization.

OS was defined as the time from the date of randomization to the date of death from any cause.

Outcome measures

Outcome measures
Measure	Arm A: Trastuzumab Emtansine n=34 Participants Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.	Arm B: Trastuzumab + Docetaxel n=15 Participants Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W. Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.
Overall Survival (OS)	NA months NA = parameter not estimable due to small number of participants included in analysis	NA months NA = parameter not estimable due to small number of participants included in analysis

SECONDARY outcome

Timeframe: At 12 months

Population: The ITT population included all randomized participants grouped according to the treatment assigned at randomization. Participants, for whom data were collected, are included in the analysis for this outcome measure.

One-year survival rate as determined by Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Arm A: Trastuzumab Emtansine n=8 Participants Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.	Arm B: Trastuzumab + Docetaxel n=8 Participants Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W. Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.
One-Year Survival Rate	92.31 percentage of participants Interval 56.64 to 98.88	100.00 percentage of participants NA = parameter not estimable due to small number of participants included in analysis

SECONDARY outcome

Timeframe: At 24 months

Population: Data for this outcome measure were not collected and are therefore not reported. The study was terminated before the time point for data collection of this outcome measure.

OS truncated at 2 years was defined as the time from the date of randomization to the date of death from any cause, with deaths occurring beyond 2 years after the participant's randomization date censored at 2 years.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At time of clinical data cut-off (up to 20 months)

ORR was defined as percentage of participants with partial response (PR) or complete response (CR) determined on the basis of investigator assessments with the use of RECIST v1.1. Tumor assessments were performed with computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest, abdomen, and pelvis. CR: disappearance of all target lesions; PR: \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response Rate (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Arm A: Trastuzumab Emtansine n=27 Participants Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.	Arm B: Trastuzumab + Docetaxel n=14 Participants Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W. Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.
Objective Response Rate (ORR)	48.1 percentage of participants Interval 28.67 to 68.05	71.4 percentage of participants Interval 41.9 to 89.6

SECONDARY outcome

Timeframe: At time of clinical data cut-off (up to 20 months)

DOR was defined as the time from the date of initial confirmed PR or CR to the date of disease progression or death within the study. CR: disappearance of all target lesions; PR: \>=30% decrease in the sum of the longest diameter of target lesions. Disease progression was defined according to RECIST, v1.1 as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Arm A: Trastuzumab Emtansine n=13 Participants Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.	Arm B: Trastuzumab + Docetaxel n=10 Participants Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W. Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.
Duration of Response (DOR)	NA months Interval 3.5 to NA = parameter not estimable due to small number of participants included in analysis	6.2 months Interval 4.1 to 11.7

SECONDARY outcome

Timeframe: Day 1, Cycle 1 (Day 1), Day 1, Cycle 2 (Day 22), Day 1, Cycle 4 (Day 64) and at study drug completion or discontinuation visit (up to 20 months)

Population: No PK analyses were performed as no participants were enrolled from China and no samples were collected.

Pharmacokinetic (PK) parameters were to be determined in a subset of participants. PK samples from the first 100 Chinese participants were planned to be collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1, Cycle 1 (Day 1), Day 1, Cycle 4 (Day 64) and at study drug completion or discontinuation visit (up to 20 months)

Population: The ITT population included all randomized participants grouped according to the treatment assigned at randomization. Only participants with at least one post-dose sample available for ATA analysis were analyzed for this outcome measure.

Outcome measures

Outcome measures
Measure	Arm A: Trastuzumab Emtansine n=33 Participants Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.	Arm B: Trastuzumab + Docetaxel Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W. Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.
Immunogenicity: Percentage of Positive Anti-Therapeutic Antibody (ATA) Response to Trastuzumab Emtansine	3.0 percentage of participants	—

SECONDARY outcome

Timeframe: On the first Day of each 21-day Cycle (Day 1, 22, 43, etc.) and at study drug completion or discontinuation visit (up to 20 months)

Population: The ITT population included all randomized participants grouped according to the treatment assigned at randomization.

The FACT-B (version 4) is a self-reported instrument which measures health-related quality of life (HRQOL) of participants with breast cancer.The FACT-B includes the breast cancer sub-scale (BCS) and is comprised of nine items specific to assessing patients' HRQOL in breast cancer.

Outcome measures

Outcome measures
Measure	Arm A: Trastuzumab Emtansine n=34 Participants Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.	Arm B: Trastuzumab + Docetaxel n=15 Participants Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W. Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 8 Day 1	16 Participants	11 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 9 Day 1	15 Participants	10 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 1 Day 1	34 Participants	15 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 2 Day 1	34 Participants	15 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 3 Day 1	33 Participants	15 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 4 Day 1	30 Participants	14 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 5 Day 1	27 Participants	13 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 6 Day 1	23 Participants	12 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 7 Day 1	18 Participants	11 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 10 Day 1	12 Participants	7 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 11 Day 1	11 Participants	7 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 12 Day 1	9 Participants	7 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 13 Day 1	8 Participants	5 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 14 Day 1	7 Participants	5 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 15 Day 1	6 Participants	4 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 16 Day 1	3 Participants	4 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 17 Day 1	2 Participants	2 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 18 Day 1	2 Participants	1 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 19 Day 1	1 Participants	1 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Cycle 20 Day 1	0 Participants	1 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Study Drug Completion/Discontinuation Visit	33 Participants	13 Participants

SECONDARY outcome

Timeframe: Days 1 and 8 of Cycles 1 and 2 and on the first day of each subsequent 21-day cycle thereafter as well as at study drug completion or discontinuation visit (up to 20 months)

Population: The ITT population included all randomized participants grouped according to the treatment assigned at randomization.

The FACT - Taxane is a self-reported instrument which measures the HRQOL of participants receiving taxane containing chemotherapy. The FACT-Taxane consists of 16 items and was designed to assess the impact of taxane treatment-related symptoms from the participant's perspective.

Outcome measures

Outcome measures
Measure	Arm A: Trastuzumab Emtansine n=34 Participants Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.	Arm B: Trastuzumab + Docetaxel n=15 Participants Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W. Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 1 Day 1	27 Participants	14 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 1 Day 8	27 Participants	15 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 2 Day 1	29 Participants	15 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 2 Day 8	29 Participants	15 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 3 Day 1	33 Participants	15 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 4 Day 1	30 Participants	14 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 5 Day 1	27 Participants	13 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 6 Day 1	23 Participants	12 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 7 Day 1	18 Participants	11 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 8 Day 1	16 Participants	11 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 9 Day 1	15 Participants	10 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 10 Day 1	12 Participants	7 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 11 Day 1	11 Participants	7 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 12 Day 1	9 Participants	7 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 13 Day 1	8 Participants	5 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 14 Day 1	7 Participants	5 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 15 Day 1	6 Participants	4 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 16 Day 1	3 Participants	4 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 17 Day 1	2 Participants	2 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 18 Day 1	2 Participants	1 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 19 Day 1	1 Participants	1 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Cycle 20 Day 1	0 Participants	1 Participants
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire Study Drug Completion/Discontinuation Visit	33 Participants	13 Participants

Adverse Events

Arm A: Trastuzumab Emtansine

Serious events: 8 serious events

Other events: 31 other events

Deaths: 0 deaths

Arm B: Trastuzumab + Docetaxel

Serious events: 5 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm A: Trastuzumab Emtansine n=34 participants at risk Participants were administered trastuzumab emtansine once every three weeks (Q3W). Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab Emtansine: Trastuzumab emtansine 3.6 milligrams/kilogram (mg/kg) was administered intravenously (IV) over 30-90 minutes Q3W.	Arm B: Trastuzumab + Docetaxel n=15 participants at risk Participants were administered trastuzumab plus docetaxel Q3W. Participants could remain on study treatment until investigator assessed disease progression, unacceptable toxicity, or Sponsor study termination occurs, whichever occurs first. Trastuzumab: For the first three-week cycle, trastuzumab was administered IV at 8 mg/kg. For subsequent cycles, trastuzumab was administered IV at 6 mg/kg Q3W. Docetaxel: Docetaxel was administered IV at either 75 milligrams/square meter (mg/m\^2) or 100 mg/m\^2 Q3W.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/34 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.	20.0% 3/15 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.
Blood and lymphatic system disorders Neutropenia	2.9% 1/34 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.	13.3% 2/15 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.
Infections and infestations Pneumonia	5.9% 2/34 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.	6.7% 1/15 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.
Infections and infestations Post procedural cellulitis	0.00% 0/34 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.	6.7% 1/15 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.
General disorders Pyrexia	5.9% 2/34 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.	0.00% 0/15 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.
Injury, poisoning and procedural complications Infusion related reaction	2.9% 1/34 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.	0.00% 0/15 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.
Metabolism and nutrition disorders Hyperammonaemia	2.9% 1/34 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.	0.00% 0/15 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.
Nervous system disorders Normal pressure hydrocephalus	0.00% 0/34 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.	6.7% 1/15 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.
Reproductive system and breast disorders Vaginal haemorrhage	2.9% 1/34 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.	0.00% 0/15 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	2.9% 1/34 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.	0.00% 0/15 • Up to 19 months The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.

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