Trial Outcomes & Findings for T-DM1 vs Paclitaxel/Trastuzumab for Breast (ATEMPT Trial) (NCT NCT01853748)

NCT ID: NCT01853748

Last Updated: 2025-03-17

Results Overview

Clinically relevant toxicities will include the composite incidence of grade 3 or higher non-hematologic toxicity, grade 2 or higher neurotoxicity, and grade 4 or higher hematologic toxicity. These toxicities will only be assessed at the pre-specified toxicity-assessment visits. In addition, the following events, regardless of timing of their occurrence, will also count towards the composite endpoint: febrile neutropenia, any toxicity requiring dose-delay, discontinuation of any study treatment (Paclitaxel, Trastuzumab, or T-DM1) for toxicity, and any serious adverse event (SAE).

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE2
• Target enrollment: 512 participants
• Primary outcome timeframe: 5 years after completion of study treatment or until death, whichever occurs first.
• Results posted on: 2025-03-17

Participant Flow

Participant milestones

Measure	Trastuzumab Emtansine (T-DM1) T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab (TH) paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments
Allocation STARTED	384	128
Allocation COMPLETED	383	114
Allocation NOT COMPLETED	1	14
Follow-Up STARTED	383	114
Follow-Up COMPLETED	293	97
Follow-Up NOT COMPLETED	90	17

Reasons for withdrawal

Measure	Trastuzumab Emtansine (T-DM1) T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab (TH) paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments
Allocation Withdrawal by Subject	1	13
Allocation not sufficient to receive intervention	0	1
Follow-Up Withdrawal by Subject	7	6
Follow-Up Adverse Event	67	7
Follow-Up not available for data collection	16	4

Baseline Characteristics

T-DM1 vs Paclitaxel/Trastuzumab for Breast (ATEMPT Trial)

Baseline characteristics by cohort

Measure	Trastuzumab Emtansine (T-DM1) n=383 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab (TH) n=114 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	Total n=497 Participants Total of all reporting groups
Age, Continuous	56 Years n=5 Participants	55 Years n=7 Participants	56 Years n=5 Participants
Sex: Female, Male Female	383 Participants n=5 Participants	114 Participants n=7 Participants	497 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	327 Participants n=5 Participants	93 Participants n=7 Participants	420 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	21 Participants n=5 Participants	7 Participants n=7 Participants	28 Participants n=5 Participants
Race/Ethnicity, Customized Asian	22 Participants n=5 Participants	4 Participants n=7 Participants	26 Participants n=5 Participants
Race/Ethnicity, Customized More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Other	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Region of Enrollment United States	383 participants n=5 Participants	114 participants n=7 Participants	497 participants n=5 Participants

PRIMARY outcome

Timeframe: 5 years after completion of study treatment or until death, whichever occurs first.

Clinically relevant toxicities will include the composite incidence of grade 3 or higher non-hematologic toxicity, grade 2 or higher neurotoxicity, and grade 4 or higher hematologic toxicity. These toxicities will only be assessed at the pre-specified toxicity-assessment visits. In addition, the following events, regardless of timing of their occurrence, will also count towards the composite endpoint: febrile neutropenia, any toxicity requiring dose-delay, discontinuation of any study treatment (Paclitaxel, Trastuzumab, or T-DM1) for toxicity, and any serious adverse event (SAE).

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=383 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=114 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Number of Participants of Clinically Relevant Toxicities (CRT) Grade 3 or higher non-hematologic toxicity	36 Participants	13 Participants	—	—
Number of Participants of Clinically Relevant Toxicities (CRT) Grade 2 or higher neurotoxicity	42 Participants	26 Participants	—	—
Number of Participants of Clinically Relevant Toxicities (CRT) Grade 4 or higher hematologic toxicity	4 Participants	0 Participants	—	—
Number of Participants of Clinically Relevant Toxicities (CRT) Febrile neutropenia	0 Participants	2 Participants	—	—
Number of Participants of Clinically Relevant Toxicities (CRT) Any toxicity requiring dose delay	106 Participants	30 Participants	—	—
Number of Participants of Clinically Relevant Toxicities (CRT) Any toxicity requiring early discontinuation of protocol therapy	67 Participants	7 Participants	—	—
Number of Participants of Clinically Relevant Toxicities (CRT) Serious adverse event	11 Participants	6 Participants	—	—

PRIMARY outcome

Timeframe: 3 years

Disease-free survival (DFS) is evaluated and defined per protocol: from the time of randomization until the to the occurrence of the first of the following events:

• Local/regional recurrence: a recurrent or new invasive ipsilateral breast cancer, invasive breast cancer in the axilla, regional lymph nodes, chest wall, or skin of the ipsilateral breast.
• Contralateral invasive breast cancer,
• Distant recurrence: metastatic disease that has either been biopsy confirmed or clinically diagnosed as recurrent invasive breast cancer. A single new lesion on a bone scan without evidence of lytic disease on x-ray and without symptoms does not in and of itself constitute distant recurrence, but multiple new bone lesions, or increased isotope uptake associated with new bone symptoms are more likely due to metastases. Bone metastases must be documented with x-rays and clinical description.
• Death from any cause

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=383 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=114 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
3-year Disease Free Survival (DFS) Rate of Trastuzumab Emtansine (TDM-1)	0.978 proportion of participants Interval 0.963 to 0.993	0.934 proportion of participants Interval 0.889 to 0.988	—	—

SECONDARY outcome

Timeframe: AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years.

All grade 3 - 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade >=3 AE of any type during the time of observation.

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=383 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=114 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Incidence Rate of Grade 3-4 Treatment-Related Toxicity	0.16 proportion of participants Interval 0.12 to 0.2	0.23 proportion of participants Interval 0.15 to 0.32	—	—

SECONDARY outcome

Timeframe: at baseline

The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below:

Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well).

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=351 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=103 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Quality of Life (QOL) FACT B Total Score at Baseline	126.25 score on a scale Standard Deviation 14.29	116.69 score on a scale Standard Deviation 19.03	—	—

SECONDARY outcome

Timeframe: at week 3

Population: not all patients required to complete the QOL

The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below:

Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well).

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=326 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=89 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Quality of Life (QOL) FACT B Total Score at Week 3	127.07 score on a scale Standard Deviation 14.52	116.6 score on a scale Standard Deviation 18.9	—	—

SECONDARY outcome

Timeframe: at week 12

Population: not all patients required to complete the QOL

The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below:

Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well).

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=302 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=83 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Quality of Life (QOL) FACT B Total Score at Week 12	124.36 score on a scale Standard Deviation 16.3	108.25 score on a scale Standard Deviation 23.33	—	—

SECONDARY outcome

Timeframe: at 6 months

Population: not all patients required to complete the QOL

The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below:

Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well).

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=299 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=83 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Quality of Life (QOL) FACT B Total Score at 6 Months	123 score on a scale Standard Deviation 16.71	118.16 score on a scale Standard Deviation 21.73	—	—

SECONDARY outcome

Timeframe: at 1 year

Population: not all patients required to complete the QOL

The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below:

Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well).

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=276 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=87 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Quality of Life (QOL) FACT B Total Score at 1 Year	123.29 score on a scale Standard Deviation 16.44	120.3 score on a scale Standard Deviation 20.88	—	—

SECONDARY outcome

Timeframe: at 18 months

Population: not all patients required to complete the QOL

The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below:

Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well).

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=279 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=77 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Quality of Life (QOL) FACT B Total Score at 18 Months	126.42 score on a scale Standard Deviation 15.67	117.93 score on a scale Standard Deviation 23.55	—	—

SECONDARY outcome

Timeframe: at 24 months

Population: not all patients required to complete the QOL

The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below:

Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well).

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=260 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=71 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Quality of Life (QOL) FACT B Total Score at 24 Months	127.19 score on a scale Standard Deviation 16.16	121.73 score on a scale Standard Deviation 22.00	—	—

SECONDARY outcome

Timeframe: Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18. The data cutoff date is 18 month.

Population: The PNQ analysis was done on patients that completed at least baseline questionnaires and at least one follow-up questionnaire. Some patients did not complete this questionnaire at either baseline or follow-up. This is the reason for the reduced number of patients when reporting PNQ results.

Neuropathy evaluated by Patient Neurotoxicity Questionnaire (PNQ) defined per protocol.

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=291 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=81 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy n=58 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy n=23 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Number of Patients Has Neuropathy Moderate to severe and severe neuropathy	24 Participants	17 Participants	22 Participants	12 Participants
Number of Patients Has Neuropathy No, mild, or moderate neuropathy	267 Participants	64 Participants	36 Participants	11 Participants

SECONDARY outcome

Timeframe: Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up.

Effects of therapy on work productivity and activity - work time missed because of health, evaluated using the Work Productivity and Activity Impairment Questionnaire (WPAI-SHP), which defined per protocol.

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=383 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=114 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Percentage of Work Time Missed Because of Health Baseline	22 percentage of time Standard Deviation 35	25 percentage of time Standard Deviation 34	—	—
Percentage of Work Time Missed Because of Health 3 weeks	13 percentage of time Standard Deviation 28	27 percentage of time Standard Deviation 36	—	—
Percentage of Work Time Missed Because of Health 12 weeks	9 percentage of time Standard Deviation 21	22 percentage of time Standard Deviation 33	—	—
Percentage of Work Time Missed Because of Health 6 months	8 percentage of time Standard Deviation 21	7 percentage of time Standard Deviation 18	—	—
Percentage of Work Time Missed Because of Health 12 months	8 percentage of time Standard Deviation 21	8 percentage of time Standard Deviation 20	—	—
Percentage of Work Time Missed Because of Health 18 months	3 percentage of time Standard Deviation 13	4 percentage of time Standard Deviation 16	—	—

SECONDARY outcome

Timeframe: Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up.

Effects of therapy on work productivity and activity - Impairment While Working because of health, evaluated using the Work Productivity and Activity Impairment Questionnaire (WPAI-SHP), which defined per protocol.

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=383 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=114 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Percentage of Impairment While Working Because of Health (Mean, SD) Baseline	10 percentage of time Standard Deviation 18	20 percentage of time Standard Deviation 26	—	—
Percentage of Impairment While Working Because of Health (Mean, SD) 3 weeks	9 percentage of time Standard Deviation 16	21 percentage of time Standard Deviation 25	—	—
Percentage of Impairment While Working Because of Health (Mean, SD) 12 weeks	11 percentage of time Standard Deviation 18	21 percentage of time Standard Deviation 26	—	—
Percentage of Impairment While Working Because of Health (Mean, SD) 6 months	9 percentage of time Standard Deviation 14	11 percentage of time Standard Deviation 19	—	—
Percentage of Impairment While Working Because of Health (Mean, SD) 12 months	12 percentage of time Standard Deviation 20	9 percentage of time Standard Deviation 18	—	—
Percentage of Impairment While Working Because of Health (Mean, SD) 18 months	3 percentage of time Standard Deviation 8	8 percentage of time Standard Deviation 17	—	—

SECONDARY outcome

Timeframe: Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up.

Effects of therapy on work productivity and activity - Work Impairment because of health, evaluated using the Work Productivity and Activity Impairment Questionnaire (WPAI-SHP), which defined per protocol.

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=383 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=114 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Percentage of Overall Work Impairment Because of Health Baseline	19 percentage of time Standard Deviation 26	31 percentage of time Standard Deviation 31	—	—
Percentage of Overall Work Impairment Because of Health 3 weeks	14 percentage of time Standard Deviation 23	30 percentage of time Standard Deviation 29	—	—
Percentage of Overall Work Impairment Because of Health 12 weeks	16 percentage of time Standard Deviation 22	29 percentage of time Standard Deviation 29	—	—
Percentage of Overall Work Impairment Because of Health 6 months	13 percentage of time Standard Deviation 18	14 percentage of time Standard Deviation 22	—	—
Percentage of Overall Work Impairment Because of Health 12 months	16 percentage of time Standard Deviation 24	13 percentage of time Standard Deviation 22	—	—
Percentage of Overall Work Impairment Because of Health 18 months	4 percentage of time Standard Deviation 12	9 percentage of time Standard Deviation 18	—	—

SECONDARY outcome

Timeframe: Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up.

Effects of therapy on work productivity and activity - Activity Impairment because of health, evaluated using the Work Productivity and Activity Impairment Questionnaire (WPAI-SHP), which defined per protocol.

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=383 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=114 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Percentage of Activity Impairment Because of Health Baseline	14 percentage of time Standard Deviation 22	22 percentage of time Standard Deviation 26	—	—
Percentage of Activity Impairment Because of Health 3 weeks	12 percentage of time Standard Deviation 19	22 percentage of time Standard Deviation 27	—	—
Percentage of Activity Impairment Because of Health 12 weeks	13 percentage of time Standard Deviation 19	33 percentage of time Standard Deviation 31	—	—
Percentage of Activity Impairment Because of Health 6 months	15 percentage of time Standard Deviation 21	17 percentage of time Standard Deviation 22	—	—
Percentage of Activity Impairment Because of Health 12 months	15 percentage of time Standard Deviation 21	14 percentage of time Standard Deviation 23	—	—
Percentage of Activity Impairment Because of Health 18 months	7 percentage of time Standard Deviation 17	15 percentage of time Standard Deviation 27	—	—

SECONDARY outcome

Timeframe: Median follow-up was 3.9 years. The AE data cutoff date is 21 April 2020.

alopecia assessment is a 5-item questionnaire that will assess the impact alopecia has had on these patients and will be conducted electronically at pre-specified study visits. If electronic evaluation is not possible, paper evaluation will be conducted.

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=383 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=114 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Number of Patients Have Alopecia	157 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: 3 years

Disease-free survival (DFS) is evaluated in patients treated with trastuzumab emtansine, which is defined per protocol: from the time of randomization until the to the occurrence of the first of the following events:

• Local/regional recurrence: a recurrent or new invasive ipsilateral breast cancer, invasive breast cancer in the axilla, regional lymph nodes, chest wall, or skin of the ipsilateral breast.
• Contralateral invasive breast cancer,
• Distant recurrence: metastatic disease that has either been biopsy confirmed or clinically diagnosed as recurrent invasive breast cancer. A single new lesion on a bone scan without evidence of lytic disease on x-ray and without symptoms does not in and of itself constitute distant recurrence, but multiple new bone lesions, or increased isotope uptake associated with new bone symptoms are more likely due to metastases. Bone metastases must be documented with x-rays and clinical description.
• Death from any cause

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=163 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=220 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
3-year T-DM1 iDFS Percentage by Tumor Size and Hormone Receptor (HR) Status	98.7 percentage of participants Interval 96.9 to 100.0	97.2 percentage of participants Interval 95.0 to 99.4	—	—

SECONDARY outcome

Timeframe: AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years.

All grade 3 - 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade >=3 AE of any type during the time of observation

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=383 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=114 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Number of Incidence of Grade 3-4 Cardiac Left Ventricular Dysfunction	3 Participants	2 Participants	—	—

SECONDARY outcome

Timeframe: AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years.

Reversible Grade 1-4 thrombocytopenia has been observed in ongoing studies with trastuzumab emtansine.

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=383 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=114 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Number of Incidence of T-DM1 Induced Grade 2-3 Thrombocytopenia	42 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: DNA sample collected at pre-treatment. AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks.

DNA will be genotyped for SNPs and CNV markers using the Infinium Human Omni1 array (1.2 million SNP platform) from Illumina. A gene-based association analyses for thrombocytopenia or bleeding is applied with significancy (p-value). This analysis was only conducted in the T-DM1 arm.

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=110 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Number of SNPs With Top Associations of Trastuzumab Emtansine-induced Grade 2-4 Thrombocytopenia in the T-DM1 Arm	54 number of SNPs	—	—	—

SECONDARY outcome

Timeframe: Surveys are took at month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up.

All grade 3 - 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade >=3 AE of any type during the time of observation.

For those who were premenopausal pre-chemotherapy, at each follow-up visit (every six months) in order to assess for duration of amenorrhea and also premature ovarian failure.

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=383 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=114 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Percentage of Patients With Amenorrhea 6 months	80 percentage of participants	21 percentage of participants	—	—
Percentage of Patients With Amenorrhea 1 year	71 percentage of participants	22 percentage of participants	—	—
Percentage of Patients With Amenorrhea 18 months	64 percentage of participants	20 percentage of participants	—	—
Percentage of Patients With Amenorrhea 24 months	74 percentage of participants	15 percentage of participants	—	—
Percentage of Patients With Amenorrhea 30 months	60 percentage of participants	11 percentage of participants	—	—
Percentage of Patients With Amenorrhea 36 months	45 percentage of participants	9 percentage of participants	—	—

SECONDARY outcome

Timeframe: After treatment

Population: no genomic data were collected using the Oncomap system

Archival tumor tissue from all patients will be assessed using a high-throughput mutation profiling system (Oncomap) to query a large panel of cancer gene mutations.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first.

OS is evaluated in patients with Stage I HER2-positive breast cancer treated with trastuzumab emtansine

Outcome measures

Measure	Trastuzumab Emtansine (T-DM1) n=383 Participants T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=114 Participants paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments	T-DM1 With Any Baseline Neuropathy T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline	TH With Any Baseline Neuropathy paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline
Median Overall Survival (OS)	NA months The cohorts have good overall survival outcome, and never reached the median survival. The overall survival rate at month 80, the longest follow up time of the cohort, is 98%. Therefore, the median survival and the corresponding 95% CI can not be estimated.	NA months The cohorts have good overall survival outcome, and never reached the median survival. The overall survival rate at month 80, the longest follow up time of the cohort, is 98%. Therefore, the median survival and the corresponding 95% CI can not be estimated.	—	—

Adverse Events

Trastuzumab Emtansine (T-DM1)

Serious events: 62 serious events

Other events: 383 other events

Deaths: 6 deaths

Paclitaxel + Trastuzumab

Serious events: 26 serious events

Other events: 114 other events

Deaths: 1 deaths

Serious adverse events

Measure	Trastuzumab Emtansine (T-DM1) n=383 participants at risk T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=114 participants at risk paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments
General disorders Infusion related reaction	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Constipation	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Diarrhea	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	2.6% 3/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Dyspepsia	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Gastric hemorrhage	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Blood and lymphatic system disorders Anemia	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Blood and lymphatic system disorders Leukocytosis	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Cardiac disorders Left ventricular systolic dysfunction	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
General disorders Fatigue	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Nausea	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Oral hemorrhage	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Vomiting	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Hepatobiliary disorders Cholecystitis	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Gum infection	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Skin infection	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Wound infection	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Alanine aminotransferase increased	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations CPK increased	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Ejection fraction decreased	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Lipase increased	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Neutrophil count decreased	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	6.1% 7/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Platelet count decreased	3.1% 12/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Weight loss	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations White blood cell decreased	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Dehydration	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Hypernatremia	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Hypokalemia	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Arthralgia	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Myalgia	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Headache	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Paresthesia	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Peripheral motor neuropathy	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	3.5% 4/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Peripheral sensory neuropathy	2.3% 9/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	5.3% 6/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Cough	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Renal and urinary disorders Hematuria	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Irregular menstruation	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Menorrhagia	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Premature menopause	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Vaginal hemorrhage	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Vascular disorders Hot flashes	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Vascular disorders Hypertension	2.1% 8/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.

Other adverse events

Measure	Trastuzumab Emtansine (T-DM1) n=383 participants at risk T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks	Paclitaxel + Trastuzumab n=114 participants at risk paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments
Investigations Creatinine increased	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	4.4% 5/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Ejection fraction decreased	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Ear and labyrinth disorders Ear pain	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Ear and labyrinth disorders Hearing impaired	1.6% 6/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Ear and labyrinth disorders Tinnitus	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Ear and labyrinth disorders Vertigo	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Ear and labyrinth disorders Vestibular disorder	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Ear and labyrinth disorders Ear and labyrinth disorders - Other	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Blood and lymphatic system disorders Anemia	13.8% 53/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	22.8% 26/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Blood and lymphatic system disorders Leukocytosis	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Blood and lymphatic system disorders Lymph node pain	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other	2.3% 9/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Cardiac disorders Atrial fibrillation	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Cardiac disorders Chest pain - cardiac	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Cardiac disorders Left ventricular systolic dysfunction	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Cardiac disorders Palpitations	3.7% 14/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	2.6% 3/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Cardiac disorders Pericardial effusion	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Cardiac disorders Restrictive cardiomyopathy	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Cardiac disorders Sinus bradycardia	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	2.6% 3/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Cardiac disorders Sinus tachycardia	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Cardiac disorders Supraventricular tachycardia	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Cardiac disorders Ventricular arrhythmia	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Cardiac disorders Ventricular tachycardia	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Cardiac disorders Cardiac disorders - Other	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
General disorders Chills	7.6% 29/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	2.6% 3/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
General disorders Edema face	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	2.6% 3/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
General disorders Edema limbs	9.1% 35/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	16.7% 19/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
General disorders Edema trunk	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
General disorders Facial pain	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
General disorders Fatigue	65.3% 250/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	70.2% 80/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
General disorders Fever	10.2% 39/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	7.9% 9/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
General disorders Flu like symptoms	6.3% 24/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	4.4% 5/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
General disorders Gait disturbance	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
General disorders Infusion related reaction	6.0% 23/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	9.6% 11/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
General disorders Injection site reaction	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
General disorders Irritability	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
General disorders Localized edema	2.9% 11/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	3.5% 4/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
General disorders Non-cardiac chest pain	3.1% 12/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
General disorders Pain	12.0% 46/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	20.2% 23/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
General disorders General disorders and administration site conditions - Other	4.4% 17/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	7.9% 9/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Alopecia	5.5% 21/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	56.1% 64/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Bullous dermatitis	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Dry skin	7.6% 29/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	13.2% 15/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Erythema multiforme	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Erythroderma	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Hypohidrosis	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Nail discoloration	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	12.3% 14/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Nail loss	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	4.4% 5/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Nail ridging	1.6% 6/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	2.6% 3/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Pain of skin	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Periorbital edema	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Photosensitivity	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Pruritus	4.7% 18/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	8.8% 10/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Rash acneiform	7.8% 30/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	14.0% 16/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Rash maculo-papular	10.2% 39/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	14.9% 17/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Scalp pain	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	3.5% 4/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	2.6% 10/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	2.6% 3/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Skin ulceration	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Telangiectasia	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Urticaria	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	13.8% 53/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	17.5% 20/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Endocrine disorders Hyperthyroidism	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Endocrine disorders Hypothyroidism	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Endocrine disorders Endocrine disorders - Other	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Abdominal distension	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Abdominal pain	7.8% 30/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	6.1% 7/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Bloating	1.8% 7/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	3.5% 4/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Cecal hemorrhage	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Colitis	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Colonic ulcer	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Constipation	29.0% 111/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	10.5% 12/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Dental caries	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Diarrhea	16.4% 63/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	47.4% 54/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Dry mouth	30.8% 118/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	5.3% 6/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Duodenal hemorrhage	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Duodenal ulcer	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Dyspepsia	12.3% 47/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	13.2% 15/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Dysphagia	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Esophagitis	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Flatulence	1.6% 6/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Gastritis	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Gastroesophageal reflux disease	12.3% 47/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	15.8% 18/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Gastrointestinal pain	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Gingival pain	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Hemorrhoidal hemorrhage	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Hemorrhoids	1.6% 6/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Mucositis oral	12.5% 48/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	13.2% 15/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Nausea	50.1% 192/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	40.4% 46/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Oral dysesthesia	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Oral hemorrhage	1.8% 7/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Oral pain	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	2.6% 3/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Periodontal disease	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Rectal hemorrhage	2.1% 8/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Stomach pain	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Tooth development disorder	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Tooth discoloration	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Toothache	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Vomiting	9.9% 38/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	11.4% 13/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Gastrointestinal disorders Gastrointestinal disorders - Other	5.0% 19/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	4.4% 5/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Hepatobiliary disorders Hepatic pain	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Hepatobiliary disorders Hepatobiliary disorders - Other	1.8% 7/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Immune system disorders Allergic reaction	2.3% 9/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Immune system disorders Cytokine release syndrome	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Immune system disorders Immune system disorders - Other	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Appendicitis	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Bladder infection	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Breast infection	1.3% 5/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Bronchial infection	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Catheter related infection	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Conjunctivitis infective	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Esophageal infection	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Eye infection	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Gum infection	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Laryngitis	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Lip infection	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Lung infection	1.3% 5/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Mucosal infection	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Nail infection	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Otitis externa	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Otitis media	1.8% 7/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Papulopustular rash	1.8% 7/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	4.4% 5/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Paronychia	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Pharyngitis	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Phlebitis infective	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Rash pustular	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Rhinitis infective	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Sepsis	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Sinusitis	3.9% 15/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	2.6% 3/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Skin infection	3.1% 12/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	6.1% 7/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Soft tissue infection	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Stoma site infection	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Tooth infection	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Upper respiratory infection	7.3% 28/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	7.9% 9/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Urinary tract infection	8.9% 34/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	2.6% 3/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Immune system disorders Vaginal infection	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Vaginal infection	1.6% 6/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Wound infection	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Infections and infestations - Other	3.4% 13/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	8.8% 10/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Infections and infestations Ankle fracture	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Injury, poisoning and procedural complications Bruising	3.9% 15/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Injury, poisoning and procedural complications Burn	1.3% 5/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Injury, poisoning and procedural complications Dermatitis radiation	11.5% 44/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	11.4% 13/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Injury, poisoning and procedural complications Fall	1.3% 5/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	4.4% 5/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Injury, poisoning and procedural complications Fracture	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	2.6% 3/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Injury, poisoning and procedural complications Intraoperative breast injury	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Injury, poisoning and procedural complications Intraoperative skin injury	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Injury, poisoning and procedural complications Radiation recall reaction (dermatologic)	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Injury, poisoning and procedural complications Seroma	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Injury, poisoning and procedural complications Spinal fracture	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Injury, poisoning and procedural complications Vascular access complication	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Injury, poisoning and procedural complications Wound complication	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Injury, poisoning and procedural complications Wrist fracture	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, specify	1.3% 5/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Alanine aminotransferase increased	29.0% 111/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	15.8% 18/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Alkaline phosphatase increased	14.9% 57/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Aspartate aminotransferase increased	33.7% 129/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	7.9% 9/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Blood bilirubin increased	9.9% 38/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	3.5% 4/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Lipase increased	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Lymphocyte count decreased	3.7% 14/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	3.5% 4/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Lymphocyte count increased	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Neutrophil count decreased	6.3% 24/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	15.8% 18/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Platelet count decreased	23.2% 89/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	4.4% 5/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Weight gain	2.1% 8/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	5.3% 6/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Weight loss	7.3% 28/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	5.3% 6/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations White blood cell decreased	6.3% 24/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	12.3% 14/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Investigations Investigations - Other, specify	2.3% 9/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	2.6% 3/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Anorexia	15.1% 58/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	12.3% 14/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Dehydration	2.6% 10/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	3.5% 4/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Glucose intolerance	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Hypercalcemia	2.3% 9/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Hyperglycemia	7.3% 28/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	5.3% 6/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Hyperkalemia	1.3% 5/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Hypernatremia	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Hypertriglyceridemia	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Hypoalbuminemia	5.0% 19/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	4.4% 5/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Hypocalcemia	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	4.4% 5/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Hypoglycemia	2.3% 9/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Hypokalemia	8.4% 32/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	3.5% 4/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Hypomagnesemia	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Hyponatremia	2.9% 11/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	3.5% 4/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Hypophosphatemia	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Arthralgia	24.5% 94/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	24.6% 28/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Arthritis	1.8% 7/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	2.6% 3/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Back pain	7.6% 29/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	10.5% 12/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Bone pain	3.4% 13/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	5.3% 6/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Chest wall pain	1.3% 5/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	2.6% 3/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Fibrosis deep connective tissue	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Flank pain	1.3% 5/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	2.3% 9/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	5.3% 6/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Growth suppression	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	2.1% 8/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Myalgia	19.6% 75/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	13.2% 15/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Neck pain	2.9% 11/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Osteoporosis	1.6% 6/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Pain in extremity	8.9% 34/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	12.3% 14/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Superficial soft tissue fibrosis	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	7.6% 29/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	4.4% 5/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Akathisia	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Amnesia	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Ataxia	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Cognitive disturbance	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Concentration impairment	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Dizziness	7.3% 28/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	13.2% 15/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Dysgeusia	14.4% 55/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	9.6% 11/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Dysphasia	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Extrapyramidal disorder	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Headache	30.8% 118/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	28.9% 33/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Hypersomnia	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Lethargy	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Leukoencephalopathy	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Memory impairment	2.1% 8/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	3.5% 4/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Paresthesia	7.3% 28/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	6.1% 7/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Peripheral motor neuropathy	6.0% 23/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	14.9% 17/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Peripheral sensory neuropathy	31.1% 119/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	43.9% 50/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Presyncope	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Sinus pain	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Spasticity	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Syncope	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Tremor	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Nervous system disorders Nervous system disorders - Other	1.8% 7/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	5.3% 6/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Eye disorders Blurred vision	6.5% 25/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	5.3% 6/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Eye disorders Cataract	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Eye disorders Conjunctivitis	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Eye disorders Dry eye	11.5% 44/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	4.4% 5/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Eye disorders Eye pain	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Eye disorders Floaters	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Eye disorders Retinal detachment	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Eye disorders Retinal tear	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Eye disorders Retinal vascular disorder	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Eye disorders Watering eyes	3.1% 12/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	2.6% 3/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Eye disorders Eye disorders - Other	4.2% 16/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	4.4% 5/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Psychiatric disorders Agitation	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Psychiatric disorders Anxiety	9.9% 38/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	20.2% 23/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Psychiatric disorders Confusion	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Psychiatric disorders Depression	8.9% 34/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	7.0% 8/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Psychiatric disorders Hallucinations	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Psychiatric disorders Insomnia	15.1% 58/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	26.3% 30/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Psychiatric disorders Libido decreased	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Psychiatric disorders Restlessness	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Psychiatric disorders Psychiatric disorders - Other	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	3.5% 4/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	5.5% 21/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	3.5% 4/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Cough	14.6% 56/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	18.4% 21/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Dyspnea	7.0% 27/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	7.0% 8/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Epistaxis	23.5% 90/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	21.9% 25/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Nasal congestion	11.7% 45/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	8.8% 10/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.6% 6/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	2.6% 3/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Postnasal drip	3.9% 15/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Productive cough	1.3% 5/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Sinus disorder	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Sleep apnea	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Sore throat	5.5% 21/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	7.0% 8/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Tracheal fistula	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Voice alteration	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other	4.4% 17/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	5.3% 6/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Renal and urinary disorders Acute kidney injury	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Renal and urinary disorders Hematuria	1.3% 5/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Renal and urinary disorders Proteinuria	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Renal and urinary disorders Renal calculi	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Renal and urinary disorders Urinary frequency	1.8% 7/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Renal and urinary disorders Urinary incontinence	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Renal and urinary disorders Urinary retention	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Renal and urinary disorders Urinary tract pain	2.1% 8/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Renal and urinary disorders Urinary urgency	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Renal and urinary disorders Renal and urinary disorders - Other	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Breast pain	8.1% 31/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	6.1% 7/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Dysmenorrhea	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Dyspareunia	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Genital edema	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Irregular menstruation	3.4% 13/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Menorrhagia	2.3% 9/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Ovarian rupture	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Pelvic pain	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Uterine hemorrhage	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Vaginal discharge	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Vaginal dryness	4.7% 18/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	7.0% 8/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Vaginal hemorrhage	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Vaginal pain	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Vaginal stricture	0.00% 0/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Reproductive system and breast disorders Reproductive system and breast disorders - Other	3.7% 14/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	1.8% 2/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Vascular disorders Flushing	1.0% 4/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	5.3% 6/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Vascular disorders Hematoma	0.78% 3/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Vascular disorders Hot flashes	15.7% 60/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	29.8% 34/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Vascular disorders Hypertension	20.4% 78/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	25.4% 29/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Vascular disorders Hypotension	0.52% 2/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.88% 1/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Vascular disorders Lymphedema	2.1% 8/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	4.4% 5/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Vascular disorders Phlebitis	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.
Vascular disorders Thromboembolic event	0.26% 1/383 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.	0.00% 0/114 • AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020.

Additional Information

Sara Tolaney, MD, MPH

Dana-Farber Cancer Institute

Phone: (877) 442-3324

Email: Sara_Tolaney@dfci.harvard.edu

Results disclosure agreements

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