Trial Outcomes & Findings for Taxane and Taxane-Induced Peripheral Neuropathy in African American Patients With Stage I-III Breast Cancer (NCT NCT04001829)

NCT ID: NCT04001829

Last Updated: 2025-11-12

Results Overview

Grade 2-4 TIPN was assessed by treating physician using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. All patients who started protocol therapy on arm A (paclitaxel) were included in the analysis. The percentage of participants with grade 2-4 TIPN was calculated based on binomial distribution and was compared between high-risk vs low-risk genotype groups using Fisher exact test. Genotype risk group (high vs. low) was determined by genotyping. High-risk genotype was defined by FCAMR GG genotype (homozygous wild type) or SBF2 mutated. Low-risk genotype was defined by carriage of at least one variant allele in FCAMR (AG or AA) and SBF2 wild-type status.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE2
• Target enrollment: 249 participants
• Primary outcome timeframe: assessed at baseline, an end of each cycle, at 6 months and 1 year post registration
• Results posted on: 2025-11-12

Participant Flow

This study was activated on June 27, 2019, first patient was enrolled on August 9, 2019. Accrual to arm A (paclitaxel) was terminated on June 4, 2021 and accrual to arm B (docetaxel) was terminated on March 31, 2022, after achieving the accrual goal on each arm separately.

Participant milestones

Measure	Arm A (paclitaxel) Patients receive paclitaxel IV over 3 hours once weekly. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive trastuzumab and/or pertuzumab per institution routine care per treating physician's discretion. Paclitaxel: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies	Arm B (docetaxel) Patients receive docetaxel IV over 1 hour once every 3 weeks. Treatment repeats every 21 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive cyclophosphamide, doxorubicin, trastuzumab, and/or pertuzumab per institution routine care per treating physician's discretion. Docetaxel: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies
Overall Study STARTED	126	123
Overall Study Received protocol therapy	121	118
Overall Study High Risk Genotype Group	91	87
Overall Study Low Risk Genotype Group	26	31
Overall Study COMPLETED	102	102
Overall Study NOT COMPLETED	24	21

Reasons for withdrawal

Measure	Arm A (paclitaxel) Patients receive paclitaxel IV over 3 hours once weekly. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive trastuzumab and/or pertuzumab per institution routine care per treating physician's discretion. Paclitaxel: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies	Arm B (docetaxel) Patients receive docetaxel IV over 1 hour once every 3 weeks. Treatment repeats every 21 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive cyclophosphamide, doxorubicin, trastuzumab, and/or pertuzumab per institution routine care per treating physician's discretion. Docetaxel: Given IV Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies
Overall Study Never start protocol therapy	5	5
Overall Study Adverse Event	11	7
Overall Study Alternative therapy	1	2
Overall Study Disease progression/relapse	2	1
Overall Study Other complicating disease	1	0
Overall Study Withdrawal by Subject	1	4
Overall Study Ineligible	2	2
Overall Study Reason missing due to delinquent data	1	0

Baseline Characteristics

Taxane and Taxane-Induced Peripheral Neuropathy in African American Patients With Stage I-III Breast Cancer

Baseline characteristics by cohort

Measure	Arm A (Paclitaxel) n=126 Participants Patients receive paclitaxel IV over 3 hours once weekly. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive trastuzumab and/or pertuzumab per institution routine care per treating physician's discretion. Paclitaxel: Given IV	Arm B (Docetaxel) n=123 Participants Patients receive docetaxel IV over 1 hour once every 3 weeks. Treatment repeats every 21 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive cyclophosphamide, doxorubicin, trastuzumab, and/or pertuzumab per institution routine care per treating physician's discretion. Docetaxel: Given IV	Total n=249 Participants Total of all reporting groups
Race (NIH/OMB) White	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants
Race (NIH/OMB) More than one race	1 Participants n=10 Participants	0 Participants n=10 Participants	1 Participants n=20 Participants
Age, Continuous	53 years n=10 Participants	56 years n=10 Participants	54 years n=20 Participants
Sex: Female, Male Female	126 Participants n=10 Participants	123 Participants n=10 Participants	249 Participants n=20 Participants
Sex: Female, Male Male	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=10 Participants	4 Participants n=10 Participants	6 Participants n=20 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	121 Participants n=10 Participants	118 Participants n=10 Participants	239 Participants n=20 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=10 Participants	1 Participants n=10 Participants	4 Participants n=20 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants
Race (NIH/OMB) Asian	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants
Race (NIH/OMB) Black or African American	125 Participants n=10 Participants	123 Participants n=10 Participants	248 Participants n=20 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants

PRIMARY outcome

Timeframe: assessed at baseline, an end of each cycle, at 6 months and 1 year post registration

Population: All patients on arm A who received at least one dose of paclitaxel and had genotyping results

Grade 2-4 TIPN was assessed by treating physician using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. All patients who started protocol therapy on arm A (paclitaxel) were included in the analysis. The percentage of participants with grade 2-4 TIPN was calculated based on binomial distribution and was compared between high-risk vs low-risk genotype groups using Fisher exact test. Genotype risk group (high vs. low) was determined by genotyping. High-risk genotype was defined by FCAMR GG genotype (homozygous wild type) or SBF2 mutated. Low-risk genotype was defined by carriage of at least one variant allele in FCAMR (AG or AA) and SBF2 wild-type status.

Outcome measures

Measure	High risk genotype group n=91 Participants Germline neuropathy risk (high vs. low) was determined by genotyping. High-risk genotype was defined by FCAMR GG genotype (homozygous wild type) or SBF2 mutated.	Low risk genotype group n=26 Participants Germline neuropathy risk (high vs. low) was determined by genotyping. Low-risk genotype was defined by carriage of at least one variant allele in FCAMR (AG or AA) and SBF2 wild-type status.
Percentage of Participants With Grade 2-4 Taxane-Induced Peripheral Neuropathy (TIPN) by Genotype Risk Group in Arm A	47 percentage of participants Interval 38.0 to 56.0	35 percentage of participants Interval 19.0 to 53.0

SECONDARY outcome

Timeframe: assessed at baseline and at end of treatment, an average of 3 months

Population: All patients who started paclitaxel and filled out the FACT/GOG-Ntx questionnaire at both baseline and end of treatment time points

The patient-reported neurotoxicity was assessed using the 11 items about neurotoxicity in the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT/GOG-Ntx) questionnaire (i.e., FACT/GOG-Ntx additional concerns subscale). The neurotoxicity total score was the sum of the scores for the 11 items, ranging from 0 to 44. Higher values of the FACT/GOG-Ntx neurotoxicity total score indicate less neurotoxicity. The FACT/GOG-Ntx neurotoxicity total score change between the baseline and at end of treatment (negative value indicates worsening symptom, positive value indicates improving symptom) was calculated and compared using two-sample t test. Genotype risk group (high vs. low) was determined by genotyping. High-risk genotype was defined by FCAMR GG genotype (homozygous wild type) or SBF2 mutated. Low-risk genotype was defined by carriage of at least one variant allele in FCAMR (AG or AA) and SBF2 wild-type status.

Outcome measures

Measure	High risk genotype group n=81 Participants Germline neuropathy risk (high vs. low) was determined by genotyping. High-risk genotype was defined by FCAMR GG genotype (homozygous wild type) or SBF2 mutated.	Low risk genotype group n=24 Participants Germline neuropathy risk (high vs. low) was determined by genotyping. Low-risk genotype was defined by carriage of at least one variant allele in FCAMR (AG or AA) and SBF2 wild-type status.
Patient-Reported Neuropathy Score Change Between Baseline and End of Treatment by Genotype Risk Group in Patients on Arm A	-7.3 score on a scale Standard Deviation 9.1	-8.1 score on a scale Standard Deviation 8.9

SECONDARY outcome

Timeframe: assessed at baseline, an end of each cycle, at 6 months and 1 year post registration

Population: All patients who received at least one dose of protocol therapy

Grade 2-4 TIPN was assessed by treating physician using CTCAE version 4.0. All patients who started protocol therapy were included in the analysis. The percentage of participants with grade 2-4 TIPN was calculated based on binomial distribution and was compared between treatment arms using Fisher exact test.

Outcome measures

Measure	High risk genotype group n=121 Participants Germline neuropathy risk (high vs. low) was determined by genotyping. High-risk genotype was defined by FCAMR GG genotype (homozygous wild type) or SBF2 mutated.	Low risk genotype group n=118 Participants Germline neuropathy risk (high vs. low) was determined by genotyping. Low-risk genotype was defined by carriage of at least one variant allele in FCAMR (AG or AA) and SBF2 wild-type status.
Percentage of Participants With Grade 2-4 TIPN Based on CTCAE Between Arm A and Arm B	44 percentage of participants Interval 36.0 to 52.0	25 percentage of participants Interval 19.0 to 33.0

SECONDARY outcome

Timeframe: Dose reduction due to TIPN was assessed at end of each cycle, up to 4 cycles in arm A and 6 cycles in arm B

Population: All patients who received at least one dose of protocol therapy

The percentage of patients with dose reduction due to TIPN was calculated as number of patients with dose reduction due to peripheral neuropathy for any dose of any cycle divided by total number of patients who started protocol therapy. The percentages were calculated along with exact 95% CI based on binomial distribution and were compared between arms using Fisher exact test.

Outcome measures

Measure	High risk genotype group n=121 Participants Germline neuropathy risk (high vs. low) was determined by genotyping. High-risk genotype was defined by FCAMR GG genotype (homozygous wild type) or SBF2 mutated.	Low risk genotype group n=118 Participants Germline neuropathy risk (high vs. low) was determined by genotyping. Low-risk genotype was defined by carriage of at least one variant allele in FCAMR (AG or AA) and SBF2 wild-type status.
Percentage of Participants With Dose Reduction Due to TIPN Between Arm A and Arm B	28 percentage of participants Interval 20.0 to 37.0	8 percentage of participants Interval 4.0 to 15.0

SECONDARY outcome

Timeframe: Dose reduction due to any reason was assessed at end of each cycle, up to 4 cycles in arm A and 6 cycles in arm B

Population: All patients who received at least one dose of protocol therapy

The percentage of patients with dose reduction due to any reason was calculated as number of patients with any dose reduction for any dose of any cycle, regardless of the reason, divided by total number of patients who started protocol therapy. The percentages were calculated along with exact 95% CI based on binomial distribution and were compared between arms using Fisher exact test.

Outcome measures

Measure	High risk genotype group n=121 Participants Germline neuropathy risk (high vs. low) was determined by genotyping. High-risk genotype was defined by FCAMR GG genotype (homozygous wild type) or SBF2 mutated.	Low risk genotype group n=118 Participants Germline neuropathy risk (high vs. low) was determined by genotyping. Low-risk genotype was defined by carriage of at least one variant allele in FCAMR (AG or AA) and SBF2 wild-type status.
Percentage of Participants With Dose Reduction Due to Any Reason Between Arm A and Arm B	39 percentage of participants Interval 30.0 to 48.0	25 percentage of participants Interval 17.0 to 33.0

SECONDARY outcome

Timeframe: assessed at baseline, at end of each cycle, at 6 months and 1 year post registration

Population: All patients who received at least one dose of docetaxel and had genotyping results

Grade 2-4 TIPN was assessed by treating physician using CTCAE version 4.0. All patients who started protocol therapy on arm B were included in the analysis. The percentage of participants with grade 2-4 TIPN was calculated based on binomial distribution and was compared between high-risk vs low-risk genotype groups using Fisher exact test. Genotype risk group (high vs. low) was determined by genotyping. High-risk genotype was defined by FCAMR GG genotype (homozygous wild type) or SBF2 mutated. Low-risk genotype was defined by carriage of at least one variant allele in FCAMR (AG or AA) and SBF2 wild-type status.

Outcome measures

Measure	High risk genotype group n=87 Participants Germline neuropathy risk (high vs. low) was determined by genotyping. High-risk genotype was defined by FCAMR GG genotype (homozygous wild type) or SBF2 mutated.	Low risk genotype group n=31 Participants Germline neuropathy risk (high vs. low) was determined by genotyping. Low-risk genotype was defined by carriage of at least one variant allele in FCAMR (AG or AA) and SBF2 wild-type status.
Percentage of Participants With Grade 2-4 TIPN by Genotype Risk Group in Arm B	28 percentage of participants Interval 20.0 to 36.0	19 percentage of participants Interval 9.0 to 35.0

Adverse Events

Arm A (paclitaxel)

Serious events: 46 serious events

Other events: 121 other events

Deaths: 7 deaths

Arm B (docetaxel)

Serious events: 61 serious events

Other events: 113 other events

Deaths: 6 deaths

Serious adverse events

Measure	Arm A (paclitaxel) n=121 participants at risk Patients receive paclitaxel IV over 3 hours once weekly. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive trastuzumab and/or pertuzumab per institution routine care per treating physician's discretion. Paclitaxel: Given IV	Arm B (docetaxel) n=118 participants at risk Patients receive docetaxel IV over 1 hour once every 3 weeks. Treatment repeats every 21 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive cyclophosphamide, doxorubicin, trastuzumab, and/or pertuzumab per institution routine care per treating physician's discretion. Docetaxel: Given IV
Blood and lymphatic system disorders Anemia	3.3% 4/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	2.5% 3/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	3.4% 4/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Blood and lymphatic system disorders Eosinophilia	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Blood and lymphatic system disorders Blood and lymphatic system disorders -Other	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Cardiac disorders Atrial fibrillation	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Cardiac disorders Chest pain - cardiac	1.7% 2/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	1.7% 2/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Cardiac disorders Myocardial infarction	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Cardiac disorders Right ventricular dysfunction	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Cardiac disorders Sinus tachycardia	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Cardiac disorders Cardiac disorders - Other	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
General disorders and administration site conditions Chills	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
General disorders and administration site conditions Edema limbs	2.5% 3/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	2.5% 3/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
General disorders and administration site conditions Fatigue	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	1.7% 2/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
General disorders and administration site conditions Fever	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	2.5% 3/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
General disorders and administration site conditions Flu like symptoms	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Injury, poisoning and procedural complications Infusion related reaction	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
General disorders and administration site conditions Non-cardiac chest pain	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	2.5% 3/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
General disorders and administration site conditions Pain	1.7% 2/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
General disorders and administration site conditions Disease progression	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
General disorders and administration site conditions Generalized edema	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
General disorders and administration site conditions General disorders and administration site conditions - Other	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	2.5% 3/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Skin and subcutaneous tissue disorders Pruritus	1.7% 2/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Skin and subcutaneous tissue disorders Rash maculo-papular	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Skin and subcutaneous tissue disorders Nail changes	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	1.7% 2/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Abdominal pain	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Anal pain	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Constipation	4.1% 5/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	4.2% 5/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Diarrhea	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	7.6% 9/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Dry mouth	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Dysphagia	1.7% 2/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Esophagitis	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Gastroesophageal reflux disease	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Mucositis oral	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	4.2% 5/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Nausea	1.7% 2/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	8.5% 10/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Stomach pain	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Vomiting	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	5.1% 6/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Gastrointestinal disorders - Other	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	3.4% 4/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Hepatobiliary disorders Gallbladder perforation	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Immune system disorders Allergic reaction	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	1.7% 2/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Immune system disorders Anaphylaxis	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Immune system disorders Immune system disorders - Other	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Infections and infestations Abdominal infection	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Infections and infestations Breast infection	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Infections and infestations Laryngitis	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	1.7% 2/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Infections and infestations Lung infection	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Infections and infestations Rash pustular	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Infections and infestations Sepsis	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Infections and infestations Skin infection	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Infections and infestations Tooth infection	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Infections and infestations Upper respiratory infection	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Infections and infestations Urinary tract infection	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	1.7% 2/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Infections and infestations Wound infection	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Infections and infestations Infections and infestations - Other	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	2.5% 3/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Injury, poisoning and procedural complications Tracheal obstruction	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Injury, poisoning and procedural complications Wound complication	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Injury, poisoning and procedural complications Wound dehiscence	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Investigations Aspartate aminotransferase increased	1.7% 2/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Investigations Creatinine increased	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	1.7% 2/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Investigations Neutrophil count decreased	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	3.4% 4/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Investigations Platelet count decreased	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	2.5% 3/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Investigations Urine output decreased	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Investigations Weight loss	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Investigations White blood cell decreased	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	2.5% 3/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Investigations Investigations - Other	1.7% 2/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	1.7% 2/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Metabolism and nutrition disorders Anorexia	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Metabolism and nutrition disorders Dehydration	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	2.5% 3/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Metabolism and nutrition disorders Hypercalcemia	1.7% 2/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Metabolism and nutrition disorders Hyperglycemia	2.5% 3/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Metabolism and nutrition disorders Hyperkalemia	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Metabolism and nutrition disorders Hyperuricemia	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Metabolism and nutrition disorders Hypoalbuminemia	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Metabolism and nutrition disorders Hypokalemia	2.5% 3/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	4.2% 5/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Metabolism and nutrition disorders Hypomagnesemia	1.7% 2/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Metabolism and nutrition disorders Hyponatremia	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Musculoskeletal and connective tissue disorders Back pain	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	2.5% 3/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Musculoskeletal and connective tissue disorders Joint range of motion decreased	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Musculoskeletal and connective tissue disorders Myalgia	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	3.4% 4/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Nervous system disorders Dizziness	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Nervous system disorders Dysgeusia	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Nervous system disorders Encephalopathy	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Nervous system disorders Headache	2.5% 3/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	1.7% 2/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Nervous system disorders Neuralgia	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Nervous system disorders Paresthesia	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	1.7% 2/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Nervous system disorders Peripheral motor neuropathy	3.3% 4/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	3.4% 4/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Nervous system disorders Peripheral sensory neuropathy	13.2% 16/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	12.7% 15/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Nervous system disorders Stroke	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Nervous system disorders Syncope	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Nervous system disorders Transient ischemic attacks	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Eye disorders Watering eyes	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Psychiatric disorders Anxiety	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Psychiatric disorders Depression	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Psychiatric disorders Insomnia	1.7% 2/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Respiratory, thoracic and mediastinal disorders Cough	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Respiratory, thoracic and mediastinal disorders Dyspnea	1.7% 2/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	2.5% 3/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Respiratory, thoracic and mediastinal disorders Sore throat	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Renal and urinary disorders Acute kidney injury	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Renal and urinary disorders Urinary retention	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Reproductive system and breast disorders Reproductive system and breast disorders - Other	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Vascular disorders Hematoma	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Vascular disorders Hot flashes	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Vascular disorders Hypertension	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Vascular disorders Hypotension	0.00% 0/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.85% 1/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Vascular disorders Lymphedema	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Vascular disorders Thromboembolic event	0.83% 1/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	0.00% 0/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis

Other adverse events

Measure	Arm A (paclitaxel) n=121 participants at risk Patients receive paclitaxel IV over 3 hours once weekly. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive trastuzumab and/or pertuzumab per institution routine care per treating physician's discretion. Paclitaxel: Given IV	Arm B (docetaxel) n=118 participants at risk Patients receive docetaxel IV over 1 hour once every 3 weeks. Treatment repeats every 21 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive cyclophosphamide, doxorubicin, trastuzumab, and/or pertuzumab per institution routine care per treating physician's discretion. Docetaxel: Given IV
Gastrointestinal disorders Gastroesophageal reflux disease	4.1% 5/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	5.1% 6/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Mucositis oral	10.7% 13/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	15.3% 18/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Nausea	28.1% 34/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	38.1% 45/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Vomiting	9.1% 11/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	9.3% 11/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Infections and infestations Infections and infestations - Other	2.5% 3/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	5.1% 6/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Investigations Alanine aminotransferase increased	17.4% 21/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	9.3% 11/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Investigations Alkaline phosphatase increased	6.6% 8/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	4.2% 5/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Investigations Aspartate aminotransferase increased	9.9% 12/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	6.8% 8/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Investigations Creatinine increased	5.0% 6/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	11.0% 13/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Investigations Lymphocyte count decreased	27.3% 33/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	11.0% 13/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Investigations Neutrophil count decreased	18.2% 22/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	11.9% 14/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Investigations Platelet count decreased	4.1% 5/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	5.9% 7/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Investigations White blood cell decreased	38.0% 46/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	25.4% 30/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Investigations Investigations - Other	5.0% 6/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	10.2% 12/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Metabolism and nutrition disorders Anorexia	10.7% 13/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	22.0% 26/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Metabolism and nutrition disorders Hyperglycemia	27.3% 33/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	29.7% 35/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Skin and subcutaneous tissue disorders Nail discoloration	12.4% 15/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	17.8% 21/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Skin and subcutaneous tissue disorders Pruritus	6.6% 8/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	11.9% 14/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Skin and subcutaneous tissue disorders Rash acneiform	5.0% 6/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	8.5% 10/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Skin and subcutaneous tissue disorders Skin hyperpigmentation	10.7% 13/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	13.6% 16/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Metabolism and nutrition disorders Hypoalbuminemia	5.8% 7/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	11.0% 13/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Skin and subcutaneous tissue disorders Nail changes	13.2% 16/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	11.0% 13/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Metabolism and nutrition disorders Hypocalcemia	5.0% 6/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	9.3% 11/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	3.3% 4/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	5.9% 7/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Abdominal pain	9.1% 11/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	4.2% 5/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Constipation	19.0% 23/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	25.4% 30/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Diarrhea	24.0% 29/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	40.7% 48/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Gastrointestinal disorders Dyspepsia	5.0% 6/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	9.3% 11/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Blood and lymphatic system disorders Anemia	57.9% 70/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	60.2% 71/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
General disorders and administration site conditions Edema limbs	6.6% 8/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	15.3% 18/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
General disorders and administration site conditions Fatigue	52.9% 64/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	63.6% 75/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
General disorders and administration site conditions Pain	19.8% 24/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	15.3% 18/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
General disorders and administration site conditions General disorders and administration site conditions - Other	5.0% 6/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	6.8% 8/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Skin and subcutaneous tissue disorders Alopecia	26.4% 32/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	43.2% 51/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Skin and subcutaneous tissue disorders Dry skin	5.8% 7/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	7.6% 9/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Metabolism and nutrition disorders Hypokalemia	11.6% 14/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	15.3% 18/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Metabolism and nutrition disorders Hyponatremia	5.8% 7/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	3.4% 4/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Musculoskeletal and connective tissue disorders Arthralgia	13.2% 16/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	19.5% 23/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Musculoskeletal and connective tissue disorders Back pain	8.3% 10/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	13.6% 16/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Musculoskeletal and connective tissue disorders Bone pain	5.8% 7/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	16.9% 20/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Musculoskeletal and connective tissue disorders Generalized muscle weakness	2.5% 3/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	5.1% 6/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Musculoskeletal and connective tissue disorders Myalgia	9.1% 11/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	16.1% 19/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Musculoskeletal and connective tissue disorders Pain in extremity	13.2% 16/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	11.9% 14/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Nervous system disorders Dizziness	8.3% 10/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	12.7% 15/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Nervous system disorders Dysgeusia	5.8% 7/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	16.1% 19/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Nervous system disorders Headache	16.5% 20/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	22.9% 27/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Nervous system disorders Paresthesia	5.8% 7/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	4.2% 5/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Nervous system disorders Peripheral motor neuropathy	21.5% 26/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	22.0% 26/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Nervous system disorders Peripheral sensory neuropathy	92.6% 112/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	77.1% 91/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Eye disorders Blurred vision	4.1% 5/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	9.3% 11/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Psychiatric disorders Anxiety	12.4% 15/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	11.9% 14/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Psychiatric disorders Depression	5.0% 6/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	8.5% 10/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Psychiatric disorders Insomnia	16.5% 20/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	17.8% 21/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Respiratory, thoracic and mediastinal disorders Cough	9.1% 11/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	7.6% 9/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Respiratory, thoracic and mediastinal disorders Dyspnea	17.4% 21/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	19.5% 23/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Reproductive system and breast disorders Breast pain	5.8% 7/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	8.5% 10/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Vascular disorders Hot flashes	14.0% 17/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	20.3% 24/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis
Vascular disorders Hypertension	17.4% 21/121 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis	22.0% 26/118 • Assessed every cycle (1 cycle=21 days) while on treatment and for 30 days after the end of treatment, then at 6 months, 1, 2 and 3 years post registration All patients are included in the all-cause mortality analysis and only treated patients are included in the AE analysis

Additional Information

Study statistician

ECOG-ACRIN Biostatistics Center

Phone: 617-632-3012

Email: eatrials@jimmy.harvard.edu

Results disclosure agreements

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

Restriction type: LTE60