Trial Outcomes & Findings for Study of Trifluridine/Tipiracil (TAS-102) in Patients With Metastatic Colorectal Cancer in Asia (NCT NCT01955837)

NCT ID: NCT01955837

Last Updated: 2020-11-17

Results Overview

The primary endpoint was Overall Survival (OS), which was defined as the time from random assignment to the date of death. In the absence of confirmation of death or for patients alive at the OS cutoff date, survival time was censored at the date of last trial follow-up or the cutoff date, whichever was earlier.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 406 participants
• Primary outcome timeframe: Every 8 weeks. Survival status should be collected for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met, whichever is later.
• Results posted on: 2020-11-17

Participant Flow

Participants were enrolled at 406 centers in China, the Republic of Korea and Thailand from 16 October 2013 to 15 June 2015.

Participant milestones

Measure	TAS-102（Trifluridine/Tipiracil） Trifluridine/Tipiracil (TAS-102) (35 mg/m2/dose) was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of TAS-102 (35mg/m2/dose) involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.	Placebo placebo was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of placebo involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.
Overall Study STARTED	271	135
Overall Study COMPLETED	271	135
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Trifluridine/Tipiracil (TAS-102) in Patients With Metastatic Colorectal Cancer in Asia

Baseline characteristics by cohort

Measure	TAS-102（Trifluridine/Tipiracil） n=271 Participants TAS-102 (35 mg/m2/dose) was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of TAS-102 (35mg/m2/dose) involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.	Placebo n=135 Participants placebo was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of placebo involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.	Total n=406 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	206 Participants n=5 Participants	103 Participants n=7 Participants	309 Participants n=5 Participants
Age, Categorical >=65 years	65 Participants n=5 Participants	32 Participants n=7 Participants	97 Participants n=5 Participants
Age, Continuous	58 years n=5 Participants	56 years n=7 Participants	57 years n=5 Participants
Sex: Female, Male Female	101 Participants n=5 Participants	51 Participants n=7 Participants	152 Participants n=5 Participants
Sex: Female, Male Male	170 Participants n=5 Participants	84 Participants n=7 Participants	254 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	271 Participants n=5 Participants	134 Participants n=7 Participants	405 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	271 Participants n=5 Participants	135 Participants n=7 Participants	406 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment South Korea	55 Participants n=5 Participants	26 Participants n=7 Participants	81 Participants n=5 Participants
Region of Enrollment China	204 Participants n=5 Participants	101 Participants n=7 Participants	305 Participants n=5 Participants
Region of Enrollment Thailand	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants

PRIMARY outcome

Timeframe: Every 8 weeks. Survival status should be collected for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met, whichever is later.

Population: The intent-to-treat (ITT) population: the ITT population was comprised of all patients who were randomized to study medication.

The primary endpoint was Overall Survival (OS), which was defined as the time from random assignment to the date of death. In the absence of confirmation of death or for patients alive at the OS cutoff date, survival time was censored at the date of last trial follow-up or the cutoff date, whichever was earlier.

Outcome measures

Measure	TAS-102（Trifluridine/Tipiracil） n=271 Participants TAS-102 (35 mg/m2/dose) was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of TAS-102 (35mg/m2/dose) involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.	Placebo n=135 Participants placebo was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of placebo involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.
Overall Survival（OS）	7.8 Months Interval 7.1 to 8.8	7.1 Months Interval 5.9 to 8.2

SECONDARY outcome

Timeframe: Every 8 weeks. Tumor assessments will be performed until radiologic progression develops or the start of new anticancer treatment, for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met.

Population: The intent-to-treat (ITT) population: the ITT population was comprised of all patients who were randomized to study medication.

Tumor assessments were performed throughout the study period and analyzed using Response Evaluation Criteria in Solid Tumors criteria (Version 1.1, 2009). Progression-free survival was defined as the time (in months) from the date of randomization until the date of the Investigator-assessed radiological disease progression or death due to any cause. Patients who received non-study cancer treatment before radiologic evidence of disease progression were censored at the date of the last evaluable tumor assessment before initiation of non-study cancer treatment.

Outcome measures

Measure	TAS-102（Trifluridine/Tipiracil） n=271 Participants TAS-102 (35 mg/m2/dose) was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of TAS-102 (35mg/m2/dose) involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.	Placebo n=135 Participants placebo was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of placebo involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.
Progression-free Survival (PFS)	2.0 Months Interval 1.9 to 2.8	1.8 Months Interval 1.7 to 1.8

SECONDARY outcome

Timeframe: From randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 30 months.

Population: The intent-to-treat (ITT) population: the ITT population was comprised of all patients who were randomized to study medication.

Time to treatment failure was defined as the time (in months) from the date of randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause. Censoring for TTF was also applied for those patients who were given non-study cancer treatment, with censoring at the time when the patient began the non-study cancer treatment.

Outcome measures

Measure	TAS-102（Trifluridine/Tipiracil） n=271 Participants TAS-102 (35 mg/m2/dose) was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of TAS-102 (35mg/m2/dose) involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.	Placebo n=135 Participants placebo was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of placebo involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.
Time to Treatment Failure (TTF)	1.9 months Interval 1.9 to 2.2	1.8 months Interval 1.7 to 1.8

SECONDARY outcome

Timeframe: From randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 30 months.

Population: The tumor response evaluable (TR) population: the TR population included all patients in the ITT population who had measurable disease (at least 1 target lesion) at baseline and with at least 1 tumor evaluation while on treatment.

The assessment of ORR was based on Investigator review of the images according to RECIST Version 1.1. Overall response rate was defined as the proportion of patients with objective evidence of complete response (CR) or partial response (PR). At the analysis stage, the best overall response was assigned for each patient as the best response recorded from all responses recorded after study randomization. If applicable, responses recorded after disease progression or initiation of non-study cancer treatment was excluded. A patient's best response assignment of stable disease (SD) needed to be maintained for at least 6 weeks after study randomization. If a patient didn't meet this condition, best response was assigned "Not evaluable".

Outcome measures

Measure	TAS-102（Trifluridine/Tipiracil） n=261 Participants TAS-102 (35 mg/m2/dose) was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of TAS-102 (35mg/m2/dose) involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.	Placebo n=130 Participants placebo was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of placebo involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.
Overall Response Rate (ORR; Complete Response [CR] or Partial Response [PR] Using RECIST Criteria)	1.1 percentage of participants Interval 0.2 to 3.3	0.0 percentage of participants Interval 0.0 to 2.8

SECONDARY outcome

Timeframe: From randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 30 months.

Population: The tumor response evaluable (TR) population: the TR population included all patients in the ITT population who had measurable disease (at least 1 target lesion) at baseline and with at least 1 tumor evaluation while on treatment.

The assessment of DCR paralleled that of ORR, with DCR defined as the proportion of patients with objective evidence of CR, PR, or SD.

Outcome measures

Measure	TAS-102（Trifluridine/Tipiracil） n=261 Participants TAS-102 (35 mg/m2/dose) was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of TAS-102 (35mg/m2/dose) involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.	Placebo n=130 Participants placebo was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of placebo involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.
Disease Control Rate (DCR; CR, PR, or Stable Disease)	44.1 percentage of participants Interval 37.9 to 50.3	14.6 percentage of participants Interval 9.0 to 21.9

SECONDARY outcome

Timeframe: From randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 30 months.

Population: The tumor response evaluable (TR) population: the TR population included all patients in the ITT population who had measurable disease (at least 1 target lesion) at baseline and with at least 1 tumor evaluation while on treatment.

Duration of response was derived for those patients with objective evidence of PR or CR. Duration of response was defined as the time from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or to death due to any cause. Patients alive and progression free as of the analysis cut-off date were censored at their last evaluable tumor response assessment prior to initiation of any non-study cancer treatment.

Outcome measures

Measure	TAS-102（Trifluridine/Tipiracil） n=261 Participants TAS-102 (35 mg/m2/dose) was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of TAS-102 (35mg/m2/dose) involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.	Placebo n=130 Participants placebo was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of placebo involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.
Duration of Response	6.6 Months Interval 3.9 to 9.2	0 Months Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: From the time a patient signed informed until 30 day safety follow-up visit or until initiation of new anticancer treatment, or assessed up to 30 months.

Population: The as-treated (AT) population: the AT population contained all patients in the ITT population who received at least 1 dose of study medication and patients were analyzed according to treatment actually received.

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-related AEs were events between administration of study drug and up to 30 Days that were absent before treatment or that worsened relative to pre-treatment state. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability /incapacity; congenital anomaly. The AEs were graded for severity using National Cancer Institute Common Terminology Criteria for AEs.

Outcome measures

Measure	TAS-102（Trifluridine/Tipiracil） n=271 Participants TAS-102 (35 mg/m2/dose) was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of TAS-102 (35mg/m2/dose) involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.	Placebo n=135 Participants placebo was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of placebo involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Adverse Events） No AEs	2 Participants	15 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Adverse Events） One or more AEs	269 Participants	120 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Adverse Events） One or more TEAEs	269 Participants	118 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Adverse Events） TEAE severity by CTCAE grade:Grade1	23 Participants	32 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Adverse Events） TEAE severity by CTCAE grade:Grade2	84 Participants	41 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Adverse Events） TEAE severity by CTCAE grade:Grade3	127 Participants	33 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Adverse Events） TEAE severity by CTCAE grade:Grade4	30 Participants	11 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Adverse Events） TEAE severity by CTCAE grade:Grade5	5 Participants	1 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Adverse Events） TEAE causality(Related)	244 Participants	70 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Adverse Events） TEAE causality(Not Related)	25 Participants	48 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Adverse Events） One or more TEAEs leading to discontinuation	27 Participants	13 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Adverse Events） One or more SAEs	63 Participants	32 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Adverse Events） One or more TESAEs	63 Participants	31 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Adverse Events） One or more TEAEs leading to death	5 Participants	1 Participants

SECONDARY outcome

Timeframe: From the time a patient signed informed until 30 day safety follow-up visit or until initiation of new anticancer treatment, or assessed up to 30 months.

Population: The as-treated (AT) population: the AT population contained all patients in the ITT population who received at least 1 dose of study medication and patients were analyzed according to treatment actually received.

All laboratory values that were out of the normal range were to be evaluated for their clinical significance before exposing the patient to the next dose of study medication. Any laboratory abnormality that was clinically significant, e.g., results in delay of study medication dosing, study discontinuation, required treatment due to abnormal values, or was considered by the Investigator to be medical important, were to be reported as an AE, unless it was considered part of clinical manifestations to a clinical diagnosis that has already been reported as an AE.

Outcome measures

Measure	TAS-102（Trifluridine/Tipiracil） n=271 Participants TAS-102 (35 mg/m2/dose) was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of TAS-102 (35mg/m2/dose) involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.	Placebo n=135 Participants placebo was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of placebo involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Lymphopenia：Grade >=3	39 Participants	3 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Anemia：Any Grade	209 Participants	52 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Anemia：Grade >=3	48 Participants	8 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Leukopenia：Any Grade	190 Participants	4 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Leukopenia：Grade >=3	56 Participants	0 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Neutropenia：Any Grade	182 Participants	1 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Neutropenia：Grade >=3	90 Participants	0 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Lymphopenia：Any Grade	146 Participants	34 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Thrombocytopenia：Any Grade	96 Participants	10 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Thrombocytopenia：Grade >=3	8 Participants	2 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Lymphocytosis：Any Grade	4 Participants	1 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Lymphocytosis：Grade >=3	1 Participants	0 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Increase in alkaline phosphatase level：Any Grade	91 Participants	58 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Increase in alkaline phosphatase level：Grade >=3	11 Participants	5 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Hyperglycemia：Any Grade	98 Participants	50 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Hyperglycemia：Grade >=3	7 Participants	3 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Increase in total bilirubin level：Any Grade	99 Participants	28 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Increase in total bilirubin level：Grade >=3	19 Participants	10 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Hypoalbuminemia：Any Grade	78 Participants	44 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Hypoalbuminemia：Grade >=3	8 Participants	0 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Hyponatremia：Any Grade	81 Participants	38 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Hyponatremia：Grade >=3	12 Participants	6 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Hypocalcemia：Any Grade	77 Participants	33 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Hypocalcemia：Grade >=3	3 Participants	1 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Increase in AST level：Any Grade	63 Participants	40 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Increase in AST level：Grade >=3	10 Participants	7 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Increase in ALT level：Any Grade	48 Participants	29 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Increase in ALT level：Grade >=3	3 Participants	4 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Hypokalemia：Any Grade	31 Participants	11 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Hypokalemia：Grade >=3	2 Participants	1 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Increase in creatinine level：Any Grade	13 Participants	10 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Increase in creatinine level：Grade >=3	3 Participants	0 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Hyperkalemia：Any Grade	11 Participants	10 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Hyperkalemia：Grade >=3	1 Participants	0 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Hypercalcemia：Any Grade	8 Participants	1 Participants
Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments（Laboratory Assessments） Hypercalcemia：Grade >=3	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Every 8 weeks. Survival status should be collected for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met, whichever is later.

Population: The intent-to-treat (ITT) population: the ITT population was comprised of all patients who were randomized to study medication.

The primary end point was OS, which was defined as the time from random assignment to the date of death. In the absence of confirmation of death or for patients alive at the OS cutoff date, survival time was censored at the date of last trial follow-up or the cutoff date, whichever was earlier.

The OS indicated above as secondary outcome was analyzed by wild type KRAS.

Outcome measures

Measure	TAS-102（Trifluridine/Tipiracil） n=271 Participants TAS-102 (35 mg/m2/dose) was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of TAS-102 (35mg/m2/dose) involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.	Placebo n=135 Participants placebo was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of placebo involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.
Overall Survival（OS）(Wild Type KRAS)	8.6 months Interval 7.4 to 10.9	7.4 months Interval 5.6 to 9.2

SECONDARY outcome

Timeframe: Every 8 weeks. Survival status should be collected for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met, whichever is later.

Population: The intent-to-treat (ITT) population: the ITT population was comprised of all patients who were randomized to study medication.

The primary end point was OS, which was defined as the time from random assignment to the date of death. In the absence of confirmation of death or for patients alive at the OS cutoff date, survival time was censored at the date of last trial follow-up or the cutoff date, whichever was earlier.

The OS indicated above as secondary outcome was analyzed by mutant type KRAS.

Outcome measures

Measure	TAS-102（Trifluridine/Tipiracil） n=271 Participants TAS-102 (35 mg/m2/dose) was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of TAS-102 (35mg/m2/dose) involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.	Placebo n=135 Participants placebo was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of placebo involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.
Overall Survival（OS）(Mutant Type KRAS)	7.0 months Interval 5.4 to 8.0	6.5 months Interval 4.6 to 7.6

SECONDARY outcome

Timeframe: Every 8 weeks. Tumor assessments will be performed until radiologic progression develops or the start of new anticancer treatment, for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met.

Population: The intent-to-treat (ITT) population: the ITT population was comprised of all patients who were randomized to study medication.

Progression-free survival was defined as the time (in months) from the date of randomization until the date of the Investigator-assessed radiological disease progression or death due to any cause. Patients who received non-study cancer treatment before radiologic evidence of disease progression were censored at the date of the last evaluable tumor assessment before initiation of non-study cancer treatment. The PFS indicated above as secondary outcome was analyzed by wild type KRAS.

Outcome measures

Measure	TAS-102（Trifluridine/Tipiracil） n=271 Participants TAS-102 (35 mg/m2/dose) was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of TAS-102 (35mg/m2/dose) involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.	Placebo n=135 Participants placebo was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of placebo involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.
Progression-free Survival (PFS) (Wild Type KRAS)	2.0 months Interval 1.9 to 3.4	1.8 months Interval 1.7 to 1.8

SECONDARY outcome

Timeframe: Every 8 weeks. Tumor assessments will be performed until radiologic progression develops or the start of new anticancer treatment, for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met.

Population: The intent-to-treat (ITT) population: the ITT population was comprised of all patients who were randomized to study medication.

Progression-free survival was defined as the time (in months) from the date of randomization until the date of the Investigator-assessed radiological disease progression or death due to any cause. Patients who received non-study cancer treatment before radiologic evidence of disease progression were censored at the date of the last evaluable tumor assessment before initiation of non-study cancer treatment. The PFS indicated above as secondary outcome was analyzed by mutant type KRAS.

Outcome measures

Measure	TAS-102（Trifluridine/Tipiracil） n=271 Participants TAS-102 (35 mg/m2/dose) was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of TAS-102 (35mg/m2/dose) involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.	Placebo n=135 Participants placebo was administered orally in continuous 28-day treatment cycles until a discontinuation criterion was met. One treatment cycle of placebo involved administration of dose twice per day, after morning and evening meals, for 5 days a week, with 2 rest days, for 2 weeks, followed by a 14-day rest period. Survival follow-up could be extended until the target number of events (288 deaths) was reached.
Progression-free Survival (PFS) (Mutant Type KRAS)	2.2 Months Interval 1.9 to 3.4	1.8 Months Interval 1.7 to 1.9

Adverse Events

TAS-102

Serious events: 63 serious events

Other events: 269 other events

Deaths: 205 deaths

Placebo

Serious events: 32 serious events

Other events: 120 other events

Deaths: 111 deaths

Serious adverse events

Measure	TAS-102 n=271 participants at risk TAS-102: TAS-102 (35 mg/m2/dose) orally, twice daily on days 1-5 and 8-12 of each 28-day cycle. Number of cycles: until at least one of the discontinuation criteria is met.	Placebo n=135 participants at risk Placebo: Placebo orally, twice daily on days 1-5 and 8-12 of each 28-day cycle. Number of cycles: until at least one of the discontinuation criteria is met.
Blood and lymphatic system disorders Anaemia	1.8% 5/271 • Number of events 5 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Blood and lymphatic system disorders Bone marrow failure	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Blood and lymphatic system disorders Granulocytopenia	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Blood and lymphatic system disorders Neutropenia	0.74% 2/271 • Number of events 2 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/271 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Abdominal pain	0.74% 2/271 • Number of events 2 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/271 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Ascites	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	2.2% 3/135 • Number of events 3 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Duodenal obstruction	0.74% 2/271 • Number of events 2 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Enterocolitis	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/271 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Ileus	0.74% 2/271 • Number of events 2 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	3.0% 4/135 • Number of events 4 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Intestinal obstruction	1.1% 3/271 • Number of events 4 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Intestinal perforation	0.00% 0/271 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Intestinal stenosis	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Nausea	0.00% 0/271 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Small intestinal obstruction	1.5% 4/271 • Number of events 7 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Vomiting	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
General disorders Asthenia	0.74% 2/271 • Number of events 2 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
General disorders Death	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
General disorders Fatigue	0.00% 0/271 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
General disorders Oedema peripheral	0.00% 0/271 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
General disorders Pyrexia	1.1% 3/271 • Number of events 4 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Hepatobiliary disorders Bile duct obstruction	0.00% 0/271 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	1.5% 2/135 • Number of events 2 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Hepatobiliary disorders Cholecystitis	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Hepatobiliary disorders Hepatic failure	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/271 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Hepatobiliary disorders Jaundice	0.74% 2/271 • Number of events 2 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Hepatobiliary disorders Jaundice cholestatic	1.1% 3/271 • Number of events 3 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Hepatobiliary disorders Liver injury	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Infections and infestations Infection	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Infections and infestations Lung infection	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Infections and infestations Pneumonia	0.74% 2/271 • Number of events 2 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	1.5% 2/135 • Number of events 2 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Infections and infestations Sepsis	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Infections and infestations Urinary tract infection	0.74% 2/271 • Number of events 2 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Investigations Blood bilirubin increased	1.1% 3/271 • Number of events 3 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/271 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	1.5% 2/135 • Number of events 2 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Metabolism and nutrition disorders Hypokalaemia	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/271 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/271 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Musculoskeletal and connective tissue disorders Bone pain	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Musculoskeletal and connective tissue disorders Flank pain	1.1% 3/271 • Number of events 3 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder neoplasm	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	1.1% 3/271 • Number of events 3 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour compression	0.00% 0/271 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Nervous system disorders Cerebral infarction	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Nervous system disorders Coma	0.00% 0/271 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Nervous system disorders Headache	0.74% 2/271 • Number of events 2 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Nervous system disorders Metabolic encephalopathy	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Renal and urinary disorders Acute kidney injury	0.74% 2/271 • Number of events 2 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Renal and urinary disorders Azotaemia	0.00% 0/271 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Renal and urinary disorders Renal impairment	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Renal and urinary disorders Urinary retention	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Reproductive system and breast disorders Pelvic pain	0.00% 0/271 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/271 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	1.5% 2/135 • Number of events 2 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Vascular disorders Deep vein thrombosis	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Vascular disorders Hypotension	0.37% 1/271 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.

Other adverse events

Measure	TAS-102 n=271 participants at risk TAS-102: TAS-102 (35 mg/m2/dose) orally, twice daily on days 1-5 and 8-12 of each 28-day cycle. Number of cycles: until at least one of the discontinuation criteria is met.	Placebo n=135 participants at risk Placebo: Placebo orally, twice daily on days 1-5 and 8-12 of each 28-day cycle. Number of cycles: until at least one of the discontinuation criteria is met.
Gastrointestinal disorders Vomiting	22.1% 60/271 • Number of events 96 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	9.6% 13/135 • Number of events 20 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Blood and lymphatic system disorders Anaemia	45.8% 124/271 • Number of events 151 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	20.0% 27/135 • Number of events 28 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Blood and lymphatic system disorders Neutropenia	36.2% 98/271 • Number of events 214 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	1.5% 2/135 • Number of events 2 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Blood and lymphatic system disorders Leukopenia	17.3% 47/271 • Number of events 94 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.74% 1/135 • Number of events 1 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Blood and lymphatic system disorders Thrombocytopenia	8.5% 23/271 • Number of events 46 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	3.0% 4/135 • Number of events 5 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Nausea	38.4% 104/271 • Number of events 164 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	14.8% 20/135 • Number of events 25 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Diarrhoea	19.9% 54/271 • Number of events 81 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	4.4% 6/135 • Number of events 6 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Abdominal pain	11.4% 31/271 • Number of events 40 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	17.8% 24/135 • Number of events 29 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Constipation	9.2% 25/271 • Number of events 33 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	14.8% 20/135 • Number of events 26 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Abdominal distension	8.5% 23/271 • Number of events 26 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	6.7% 9/135 • Number of events 9 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Dyspepsia	5.5% 15/271 • Number of events 19 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	3.0% 4/135 • Number of events 4 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Abdominal pain upper	3.7% 10/271 • Number of events 12 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	5.2% 7/135 • Number of events 9 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
General disorders Fatigue	25.5% 69/271 • Number of events 92 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	14.8% 20/135 • Number of events 20 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
General disorders Asthenia	10.7% 29/271 • Number of events 35 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	8.1% 11/135 • Number of events 11 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
General disorders Pyrexia	6.6% 18/271 • Number of events 20 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	7.4% 10/135 • Number of events 12 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Infections and infestations Upper respiratory tract infection	5.2% 14/271 • Number of events 17 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	2.2% 3/135 • Number of events 5 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Investigations White blood cell count decreased	37.6% 102/271 • Number of events 233 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	2.2% 3/135 • Number of events 3 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Investigations Neutrophil count decreased	27.7% 75/271 • Number of events 191 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	0.00% 0/135 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Investigations Blood bilirubin increased	19.6% 53/271 • Number of events 77 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	8.9% 12/135 • Number of events 13 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Investigations Aspartate aminotransferase increased	12.2% 33/271 • Number of events 40 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	14.8% 20/135 • Number of events 20 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Investigations Platelet count decreased	15.5% 42/271 • Number of events 75 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	1.5% 2/135 • Number of events 2 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Investigations Alanine aminotransferase increased	9.2% 25/271 • Number of events 32 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	11.9% 16/135 • Number of events 17 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Investigations Blood alkaline phosphatase increased	7.7% 21/271 • Number of events 22 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	11.1% 15/135 • Number of events 15 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Investigations Bilirubin conjugated increased	6.3% 17/271 • Number of events 30 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	3.0% 4/135 • Number of events 4 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Investigations Haemoglobin decreased	6.6% 18/271 • Number of events 20 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	2.2% 3/135 • Number of events 5 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Investigations Gamma-glutamyltransferase increased	3.7% 10/271 • Number of events 10 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	6.7% 9/135 • Number of events 9 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Metabolism and nutrition disorders Decreased appetite	29.9% 81/271 • Number of events 105 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	16.3% 22/135 • Number of events 25 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Metabolism and nutrition disorders Hypoalbuminaemia	5.2% 14/271 • Number of events 14 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	9.6% 13/135 • Number of events 13 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Metabolism and nutrition disorders Hyperglycaemia	5.2% 14/271 • Number of events 16 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	3.0% 4/135 • Number of events 4 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Metabolism and nutrition disorders Hyponatraemia	2.6% 7/271 • Number of events 7 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	5.9% 8/135 • Number of events 8 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Musculoskeletal and connective tissue disorders Back pain	6.6% 18/271 • Number of events 18 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	9.6% 13/135 • Number of events 13 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Nervous system disorders Dizziness	9.2% 25/271 • Number of events 34 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	4.4% 6/135 • Number of events 6 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Nervous system disorders Headache	5.2% 14/271 • Number of events 15 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	3.0% 4/135 • Number of events 4 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Respiratory, thoracic and mediastinal disorders Cough	4.8% 13/271 • Number of events 14 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	7.4% 10/135 • Number of events 11 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.1% 11/271 • Number of events 11 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.	5.9% 8/135 • Number of events 8 • Safety monitoring continued from the time a patient signed informed until 30 days after the last dose of study medication or until the initiation of another cancer therapy, whichever came first, up to 30 months. An AE was any untoward medical condition that occurred in a patient while participating in a clinical study and did not necessarily have a causal relationship with the use of the product. Treatment-emergent adverse events (TEAEs) were AEs that occurred from the initiation of any study medication administration and did not necessarily have a causal relationship to the use of the study medication.

Additional Information

Taiho Pharmaceutical Co., Ltd.

Clinical Trial Registration Contact

Email: toiawase@taiho.co.jp

Results disclosure agreements

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

Restriction type: OTHER