Trial Outcomes & Findings for A Study of Trastuzumab Emtansine in Comparison With Treatment of Physician's Choice in Participants With HER2-positive Breast Cancer Who Have Received at Least Two Prior Regimens of HER2-directed Therapy (NCT NCT01419197)

NCT ID: NCT01419197

Last Updated: 2016-10-12

Results Overview

Progression-free survival was defined as the time from randomization to the first documented disease progression by investigator assessment using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death from any cause, whichever occurred first. Progression-free survival was a co-primary endpoint.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 602 participants
• Primary outcome timeframe: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)
• Results posted on: 2016-10-12

Participant Flow

A total of 602 patients were randomized to the study (404 to receive Trastuzumab Emtansine and 198 to receive Treatment of Physician's Choice).

Participant milestones

Measure	Trastuzumab Emtansine Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.	Treatment of Physician's Choice Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and human epidermal growth factor receptor 2 (HER2)-directed therapy.
Overall Study STARTED	404	198
Overall Study Switched to Trastuzumab Emtansine	0	94
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	404	198

Reasons for withdrawal

Measure	Trastuzumab Emtansine Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.	Treatment of Physician's Choice Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and human epidermal growth factor receptor 2 (HER2)-directed therapy.
Overall Study Death	247	122
Overall Study Physician Decision	4	4
Overall Study Non-compliance	3	1
Overall Study Withdrawal by Subject	33	32
Overall Study Study Completed by Sponsor	103	34
Overall Study Reason Not Specified	0	1
Overall Study Lost to Follow-up	14	4

Baseline Characteristics

A Study of Trastuzumab Emtansine in Comparison With Treatment of Physician's Choice in Participants With HER2-positive Breast Cancer Who Have Received at Least Two Prior Regimens of HER2-directed Therapy

Baseline characteristics by cohort

Measure	Trastuzumab Emtansine n=404 Participants Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.	Treatment of Physician's Choice n=198 Participants Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.	Total n=602 Participants Total of all reporting groups
Age, Continuous	53.3 years STANDARD_DEVIATION 10.4 • n=5 Participants	54.3 years STANDARD_DEVIATION 10.8 • n=7 Participants	53.6 years STANDARD_DEVIATION 10.5 • n=5 Participants
Sex: Female, Male Female	401 Participants n=5 Participants	197 Participants n=7 Participants	598 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

Population: Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.

Progression-free survival was defined as the time from randomization to the first documented disease progression by investigator assessment using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death from any cause, whichever occurred first. Progression-free survival was a co-primary endpoint.

Outcome measures

Measure	Trastuzumab Emtansine n=404 Participants Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.	Treatment of Physician's Choice n=198 Participants Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Progression-free Survival	6.2 Months Interval 5.59 to 6.87	3.3 Months Interval 2.89 to 4.14

PRIMARY outcome

Timeframe: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

Population: Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.

Overall survival (OS) was defined as the time from randomization to death from any cause. Overall survival was a co-primary endpoint.

Outcome measures

Measure	Trastuzumab Emtansine n=404 Participants Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.	Treatment of Physician's Choice n=198 Participants Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Overall Survival	NA Months Interval 13.14 to The median and the upper limit of the confidence interval could not be estimated due to too few events.	14.9 Months Interval 11.27 to The upper limit of the confidence interval could not be estimated due to too few events.

SECONDARY outcome

Timeframe: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

Population: Randomized population: All participants who were randomized to the study. Only participants with measurable disease at Baseline were included in the analysis. Participants were included in the treatment group to which they were randomized.

An objective response was defined as a complete or partial response determined on 2 consecutive occasions ≥ 4 weeks apart using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must be < 10 mm on the short axis. Partial response was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum. Participants who had no post-baseline tumor assessment were counted as non-responders.

Outcome measures

Measure	Trastuzumab Emtansine n=345 Participants Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.	Treatment of Physician's Choice n=163 Participants Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Percentage of Participants With an Objective Response	31.3 Percentage of participants Interval 26.5 to 36.5	8.6 Percentage of participants Interval 5.1 to 13.8

SECONDARY outcome

Timeframe: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

Population: Randomized population: All participants who were randomized to the study. Only participants with an objective response were included in the analysis. Participants were included in the treatment group to which they were randomized.

Duration of the objective response was defined as the time from the first tumor assessment that was judged to indicate that the patient had an objective response to the time of first documented disease progression using RECIST v1.1 per investigator assessment or death from any cause, whichever occurred first.

Outcome measures

Measure	Trastuzumab Emtansine n=108 Participants Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.	Treatment of Physician's Choice n=14 Participants Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Duration of the Objective Response	9.7 Months Interval 6.6 to 10.51	NA Months Interval 2.4 to The median and the upper confidence interval value could not be estimated due to too few events.

SECONDARY outcome

Timeframe: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

Population: Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.

6-month and 1-year survival were defined as the percentage of participants who were alive at 6 months and 1 year, respectively, as estimated using Kaplan-Meier method.

Outcome measures

Measure	Trastuzumab Emtansine n=404 Participants Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.	Treatment of Physician's Choice n=198 Participants Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
6-month and 1-year Survival 6-Month Survival	90.9 Percentage of participants Interval 87.79 to 94.01	78.3 Percentage of participants Interval 71.49 to 85.19
6-month and 1-year Survival 1-Year Survival	68.6 Percentage of participants Interval 59.91 to 77.28	56.9 Percentage of participants Interval 42.22 to 71.63

SECONDARY outcome

Timeframe: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

Population: Randomized population: All participants who were randomized to the study. Only participants with a Baseline pain score and at least 1 post-baseline pain score were included in the analysis. Participants were included in the treatment group to which they were randomized.

Time to pain symptom progression was defined as the time from randomization to the first documentation of an increase in narcotic use and/or a 10 point increase from Baseline in the pain score as measured by the European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire for patients with bone metastases (EORTC QLQ-BM22). The EORTC QLQ-BM22 assesses the symptoms of bone metastases using 22 items: 5 items for sites of pain, 3 pain characteristics, 8 functional interference aspects, and 6 psychosocial aspects. The pain score was derived from the 3 pain characteristic items. Each item was rated on a 4-point scale, where 1=Not at all to 4=Very much. The pain score was the sum of the 3 pain characteristic scores and was normalized to a scale of 0 to 100. A higher score indicates greater pain.

Outcome measures

Measure	Trastuzumab Emtansine n=297 Participants Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.	Treatment of Physician's Choice n=117 Participants Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Time to Pain Symptom Progression	2.9 Months Interval 2.2 to 3.7	3.6 Months Interval 2.7 to 4.5

SECONDARY outcome

Timeframe: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years)

Population: Randomized population: All participants who were randomized to the study. Only participants with a Baseline pain score and at least 1 post-baseline pain score were included in the analysis. Participants were included in the treatment group to which they were randomized.

The EORTC QLQ-BM22 assesses the symptoms of bone metastases using 22 items: 5 items for sites of pain, 3 pain characteristics, 8 functional interference aspects, and 6 psychosocial aspects. The pain score was derived from the 3 pain characteristic items. Each item was rated on a 4-point scale, where 1=Not at all to 4=Very much. The pain score was the sum of the 3 pain characteristic scores and was normalized to a scale of 0 to 100. A higher score indicates greater pain. A negative change score indicates improvement.

Outcome measures

Measure	Trastuzumab Emtansine n=297 Participants Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.	Treatment of Physician's Choice n=117 Participants Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 20 (n=4,0)	-5.6 Units on a scale Standard Deviation 23.1	NA Units on a scale Standard Deviation NA There were no participants with available data.
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 2 (n=282,98)	-3.4 Units on a scale Standard Deviation 21.1	-9.4 Units on a scale Standard Deviation 22.1
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 3 (n=257,86)	-4.6 Units on a scale Standard Deviation 21.1	-6.1 Units on a scale Standard Deviation 21.4
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 4 (n=236,74)	-4.8 Units on a scale Standard Deviation 19.6	-3.8 Units on a scale Standard Deviation 24.1
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 5 (n=224,54)	-6.6 Units on a scale Standard Deviation 22.8	-2.7 Units on a scale Standard Deviation 18.9
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 6 (n=195,42)	-4.8 Units on a scale Standard Deviation 23.5	2.4 Units on a scale Standard Deviation 17.1
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 7 (n=163,30)	-4.2 Units on a scale Standard Deviation 23.8	-1.5 Units on a scale Standard Deviation 15.6
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 8 (n=130,20)	-7.0 Units on a scale Standard Deviation 21.0	2.2 Units on a scale Standard Deviation 18.6
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 9 (n=97,15)	-5.8 Units on a scale Standard Deviation 22.2	6.7 Units on a scale Standard Deviation 20.1
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 10 (n=80,7)	-8.9 Units on a scale Standard Deviation 21.2	1.6 Units on a scale Standard Deviation 11.9
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 11 (n=56,8)	-10.5 Units on a scale Standard Deviation 23.1	0.0 Units on a scale Standard Deviation 8.4
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 12 (n=48,7)	-11.3 Units on a scale Standard Deviation 25.8	1.6 Units on a scale Standard Deviation 7.7
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 13 (n=40,5)	-10.0 Units on a scale Standard Deviation 23.3	2.2 Units on a scale Standard Deviation 12.2
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 14 (n=33,5)	-10.1 Units on a scale Standard Deviation 21.8	0.0 Units on a scale Standard Deviation 7.9
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 15 (n=27,3)	-13.2 Units on a scale Standard Deviation 22.0	0.0 Units on a scale Standard Deviation 0.0
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 16 (n=19,3)	-12.3 Units on a scale Standard Deviation 19.6	-3.7 Units on a scale Standard Deviation 6.4
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 17 (n=15,2)	-7.4 Units on a scale Standard Deviation 22.9	-5.6 Units on a scale Standard Deviation 7.9
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 18 (n=11,0)	-9.1 Units on a scale Standard Deviation 12.0	NA Units on a scale Standard Deviation NA There were no participants with available data.
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 19 (n=8,0)	1.4 Units on a scale Standard Deviation 9.3	NA Units on a scale Standard Deviation NA There were no participants with available data.
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Cycle 21 (n=3,0)	-3.7 Units on a scale Standard Deviation 6.4	NA Units on a scale Standard Deviation NA There were no participants with available data.
Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle Termination Visit (n=84,37)	-1.6 Units on a scale Standard Deviation 21.8	-9.0 Units on a scale Standard Deviation 23.3

SECONDARY outcome

Timeframe: Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)

Population: Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.

Overall survival was defined as the time from randomization to death from any cause.

Outcome measures

Measure	Trastuzumab Emtansine n=404 Participants Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.	Treatment of Physician's Choice n=198 Participants Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
Overall Survival (Final Analysis)	22.7 Months Interval 19.35 to 27.47	15.8 Months Interval 13.5 to 18.66

SECONDARY outcome

Timeframe: Baseline to the clinical cut-off date of 13 Feb 2015 (up to 4 years)

Population: Randomized population: All participants who were randomized to the study. Participants were included in the treatment group to which they were randomized.

6-month and 1-year survival were defined as the percentage of participants who were alive at 6 months and 1 year, respectively, as estimated using Kaplan-Meier method.

Outcome measures

Measure	Trastuzumab Emtansine n=404 Participants Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.	Treatment of Physician's Choice n=198 Participants Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.
6-month and 1-year Survival (Final Analysis) 6-Month Survival	91.3 Percentage of participants Interval 88.52 to 94.11	78.9 Percentage of participants Interval 72.78 to 85.04
6-month and 1-year Survival (Final Analysis) 1-Year Survival	76.5 Percentage of participants Interval 72.23 to 80.79	65.6 Percentage of participants Interval 58.36 to 72.76

Adverse Events

Trastuzumab Emtansine

Serious events: 102 serious events

Other events: 371 other events

Deaths: 0 deaths

Treatment of Physician's Choice (TPC)

Serious events: 41 serious events

Other events: 148 other events

Deaths: 0 deaths

Trastuzumab Emtansine - Post TPC Treatment Switch

Serious events: 19 serious events

Other events: 74 other events

Deaths: 0 deaths

Serious adverse events

Measure	Trastuzumab Emtansine n=403 participants at risk Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.	Treatment of Physician's Choice (TPC) n=184 participants at risk Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.	Trastuzumab Emtansine - Post TPC Treatment Switch n=94 participants at risk Participants, who switched treatment in the Treatment of Physician's Choice arm to trastuzumab emtansine, were administered trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
Blood and lymphatic system disorders Anaemia	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 2/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Blood and lymphatic system disorders Febrile neutropenia	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	3.8% 7/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Blood and lymphatic system disorders Granulocytopenia	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Blood and lymphatic system disorders Neutropenia	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 2/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Blood and lymphatic system disorders Thrombocytopenia	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Cardiac disorders Cardiac failure	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Ear and labyrinth disorders Vertigo	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Endocrine disorders Hypercalcaemia of malignancy	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Eye disorders Vision blurred	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Abdominal discomfort	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Abdominal pain	0.99% 4/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.6% 3/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Abdominal pain upper	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Abdominal wall haematoma	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Colitis	0.50% 2/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Diarrhoea	0.50% 2/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Gastric haemorrhage	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Ileus	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Nausea	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 2/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Obstruction gastric	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Pancreatitis	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Proctitis Haemorrhagic	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Small intestinal obstruction	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Vomiting	0.50% 2/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 2/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Adverse drug reaction	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Asthenia	0.74% 3/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Death	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Device occlusion	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Fatigue	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders General physical health deterioration	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Malaise	0.50% 2/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Non-cardiac chest pain	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Oedema peripheral	0.50% 2/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 2/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Pain	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Pyrexia	1.7% 7/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 2/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Vessel puncture site haemorrhage	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Hepatobiliary disorders Bile duct obstruction	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Hepatobiliary disorders Cholangitis	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Hepatobiliary disorders Cholecystitis	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Hepatobiliary disorders Nodular regenerative hyperplasia	0.74% 3/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Immune system disorders Drug hypersensitivity	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Immune system disorders Hypersensitivity	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Appendicitis	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Bronchopneumonia	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Cellulitis	0.50% 2/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	2.2% 4/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Clostridium bacteraemia	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Device related infection	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Device related sepsis	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Gastroenteritis	0.50% 2/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Infected fistula	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Infection	0.50% 2/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Infectious colitis	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Lung infection	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Lymphangitis	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Mastitis	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Neutropenic sepsis	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Pharyngotonsillitis	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Pneumonia	1.2% 5/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Postoperative wound infection	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Sepsis	0.74% 3/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Sinusitis	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Tracheitis	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Upper respiratory tract infection	0.50% 2/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Urinary tract infection	0.99% 4/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Urosepsis	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Viral upper respiratory tract infection	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Wound infection	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Injury, poisoning and procedural complications Fall	0.50% 2/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Injury, poisoning and procedural complications Femoral neck fracture	0.50% 2/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Injury, poisoning and procedural complications Femur fracture	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Injury, poisoning and procedural complications Infusion related reaction	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Injury, poisoning and procedural complications Sternal fracture	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Injury, poisoning and procedural complications Subdural haematoma	0.50% 2/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Injury, poisoning and procedural complications Subdural haemorrhage	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Injury, poisoning and procedural complications Traumatic intracranial haemorrhage	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Injury, poisoning and procedural complications Wound decomposition	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Injury, poisoning and procedural complications Wound haemorrhage	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Investigations Transaminases increased	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Investigations White blood cell count decreased	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Metabolism and nutrition disorders Decreased appetite	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Metabolism and nutrition disorders Dehydration	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Metabolism and nutrition disorders Hypercalcaemia	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Metabolism and nutrition disorders Hyperglycaemia	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Metabolism and nutrition disorders Hypokalaemia	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Metabolism and nutrition disorders Hyponatraemia	0.99% 4/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Metabolism and nutrition disorders Hypophagia	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Metabolism and nutrition disorders Malnutrition	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Musculoskeletal and connective tissue disorders Arthralgia	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Musculoskeletal and connective tissue disorders Back pain	0.50% 2/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Musculoskeletal and connective tissue disorders Muscle haemorrhage	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Musculoskeletal and connective tissue disorders Spinal pain	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenocarcinoma	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.50% 2/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Ataxia	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Brain oedema	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Cerebral haematoma	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Cerebral haemorrhage	0.50% 2/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Cognitive disorder	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Depressed level of consciousness	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Dizziness	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Haemorrhage intracranial	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Hepatic encephalopathy	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Loss of consciousness	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Paraesthesia	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Paraparesis	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Seizure	1.2% 5/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Somnolence	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Subarachnoid haemorrhage	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Transient ischaemic attack	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Visual field defect	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Psychiatric disorders Confusional state	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Renal and urinary disorders Haematuria	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Reproductive system and breast disorders Vaginal haemorrhage	0.50% 2/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.5% 6/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	2.7% 5/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	2.1% 2/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Respiratory, thoracic and mediastinal disorders Epistaxis	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Respiratory, thoracic and mediastinal disorders Non-cardiogenic pulmonary oedema	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Respiratory, thoracic and mediastinal disorders Obliterative bronchiolitis	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.74% 3/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 2/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.50% 2/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 2/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Vascular disorders Deep vein thrombosis	0.50% 2/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Vascular disorders Embolism	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Vascular disorders Embolism venous	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Vascular disorders Hypertensive crisis	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Vascular disorders Hypotension	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Vascular disorders Lymphoedema	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.54% 1/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Vascular disorders Superior vena cava syndrome	0.25% 1/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Hepatobiliary disorders Hepatotoxicity	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Abdominal infection	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Abscess	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Biliary tract infection	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Injury, poisoning and procedural complications Toxicity to various agents	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour necrosis	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Epilepsy	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Hemiplegia	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Respiratory, thoracic and mediastinal disorders Pulmonary Fibrosis	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 1/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).

Other adverse events

Measure	Trastuzumab Emtansine n=403 participants at risk Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.	Treatment of Physician's Choice (TPC) n=184 participants at risk Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.	Trastuzumab Emtansine - Post TPC Treatment Switch n=94 participants at risk Participants, who switched treatment in the Treatment of Physician's Choice arm to trastuzumab emtansine, were administered trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
Blood and lymphatic system disorders Anaemia	11.2% 45/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	10.3% 19/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	7.4% 7/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Blood and lymphatic system disorders Leukopenia	2.2% 9/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	6.0% 11/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Blood and lymphatic system disorders Neutropenia	7.4% 30/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	21.2% 39/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	5.3% 5/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Blood and lymphatic system disorders Thrombocytopenia	20.1% 81/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	3.3% 6/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	18.1% 17/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Abdominal pain	6.7% 27/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	10.9% 20/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	9.6% 9/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Constipation	22.3% 90/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	17.4% 32/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	7.4% 7/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Diarrhoea	12.9% 52/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	21.7% 40/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	10.6% 10/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Dry mouth	12.7% 51/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 2/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	9.6% 9/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Dyspepsia	5.2% 21/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	6.5% 12/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Gingival bleeding	5.2% 21/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Nausea	35.7% 144/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	21.7% 40/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	17.0% 16/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Stomatitis	3.2% 13/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	6.0% 11/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Vomiting	19.1% 77/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	8.7% 16/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	10.6% 10/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Asthenia	18.9% 76/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	17.9% 33/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	16.0% 15/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Chills	5.2% 21/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	2.2% 4/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Fatigue	30.5% 123/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	26.1% 48/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	10.6% 10/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Influenza like illness	5.2% 21/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 2/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Mucosal inflammation	4.2% 17/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	5.4% 10/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	7.4% 7/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Oedema peripheral	6.5% 26/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	6.0% 11/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Pyrexia	19.1% 77/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	12.0% 22/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	14.9% 14/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Nasopharyngitis	8.7% 35/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	6.5% 12/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	6.4% 6/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Upper respiratory tract infection	8.7% 35/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	4.3% 8/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	8.5% 8/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Urinary tract infection	6.5% 26/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	3.8% 7/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	9.6% 9/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Investigations Alanine aminotransferase increased	9.4% 38/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	5.4% 10/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	7.4% 7/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Investigations Aspartate aminotransferase increased	12.7% 51/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	7.1% 13/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	13.8% 13/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Investigations Blood alkaline phosphatase increased	5.2% 21/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	2.7% 5/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	7.4% 7/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Investigations Blood bilirubin increased	9.4% 38/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	1.1% 2/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	5.3% 5/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Investigations Ejection fraction decreased	2.7% 11/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	6.5% 12/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Metabolism and nutrition disorders Decreased appetite	16.4% 66/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	13.6% 25/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	16.0% 15/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Metabolism and nutrition disorders Hypokalaemia	7.4% 30/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	2.2% 4/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	6.4% 6/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Musculoskeletal and connective tissue disorders Arthralgia	14.9% 60/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	4.3% 8/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	7.4% 7/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Musculoskeletal and connective tissue disorders Back pain	8.7% 35/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	7.1% 13/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	6.4% 6/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Musculoskeletal and connective tissue disorders Bone pain	5.5% 22/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	3.8% 7/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Musculoskeletal and connective tissue disorders Muscle spasms	6.5% 26/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	4.9% 9/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	4.5% 18/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	5.4% 10/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	7.4% 7/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Musculoskeletal and connective tissue disorders Myalgia	11.7% 47/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	7.6% 14/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	6.4% 6/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Musculoskeletal and connective tissue disorders Pain in extremity	10.9% 44/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	4.9% 9/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Dizziness	7.7% 31/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	3.3% 6/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	6.4% 6/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Headache	24.8% 100/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	12.0% 22/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	17.0% 16/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Neuropathy peripheral	5.0% 20/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	5.4% 10/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	7.4% 7/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Nervous system disorders Paraesthesia	6.9% 28/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	6.0% 11/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	9.6% 9/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Psychiatric disorders Insomnia	8.7% 35/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	3.3% 6/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	8.5% 8/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Respiratory, thoracic and mediastinal disorders Cough	18.9% 76/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	13.0% 24/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	12.8% 12/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.4% 42/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	11.4% 21/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	6.4% 6/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Respiratory, thoracic and mediastinal disorders Epistaxis	16.6% 67/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	3.8% 7/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	12.8% 12/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Skin and subcutaneous tissue disorders Alopecia	2.2% 9/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	10.9% 20/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Skin and subcutaneous tissue disorders Pruritus	5.7% 23/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	9.2% 17/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Skin and subcutaneous tissue disorders Rash	6.7% 27/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	10.3% 19/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Eye disorders Lacrimation increased	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	5.3% 5/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Gastrointestinal disorders Abdominal pain upper	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	7.4% 7/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
General disorders Pain	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	5.3% 5/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Infections and infestations Sinusitis	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	5.3% 5/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/403 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	0.00% 0/184 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).	5.3% 5/94 • Adverse events were collected from treatment initiation until 30 days following the last administration of study drug or study discontinuation on 31 August 2015 (up to approximately 4 years). Safety population: All participants who received any amount of planned study treatment, according to treatment actually received. Data for participants in the Treatment of Physicians Choice (TPC) arm who switched treatment to receive trastuzumab emtansine (TE) following disease progression on TPC are presented separately. Median treatment duration of trastuzumab emtansine: 5.2 months (range 0.03-40.7),TPC: 2.7 months (range 0.03-31.0) and TE - Post TPC Treatment Switch: 4.5 months (range 1-43).

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

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