Trial Outcomes & Findings for Phase III Study of TAS-118 Plus Oxaliplatin Versus S-1 Plus Cisplatin in Patients With Advanced Gastric Cancer (NCT NCT02322593)

Last Updated: 2021-12-20

Results Overview

The primary endpoint was OS, which was defined as the time from the date of randomization to the date of death from any cause. Surviving patients were censored at the cutoff date or last contact date if lost to follow-up, or upon withdrawal of consent.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

711 participants

Primary outcome timeframe

A survival follow-up was required every 12 weeks from the date of randomization to the date of death from any cause, whichever came first, assessed up to 38 months.

Results posted on

2021-12-20

Participant Flow

Participant milestones

Participant milestones
Measure	TAS-118/Oxaliplatin TAS-118 plus Oxaliplatin L-OHP was administered intravenously at dose of 85 mg/m2 on day 1, and TAS-118 were administered 30-60 mg orally twice daily for 7 days (day 1 through day 7), repeated every 2 weeks. Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met.	S-1/Cisplatin S-1 plus Cisplatin CDDP was administered intravenously at dose of 60 mg/m2 on day 1 (Korea) or day 8 (Japan), and S-1 were administered 40-60 mg orally twice daily for 21 days (day 1 through day 21), repeated every 5 weeks (rest period can be shorten from 14 days to 7 days). Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met.
Overall Study STARTED	356	355
Overall Study COMPLETED	356	355
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase III Study of TAS-118 Plus Oxaliplatin Versus S-1 Plus Cisplatin in Patients With Advanced Gastric Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TAS-118/Oxaliplatin n=347 Participants TAS-118 plus Oxaliplatin L-OHP was administered intravenously at dose of 85 mg/m2 on day 1, and TAS-118 were administered 30-60 mg orally twice daily for 7 days (day 1 through day 7), repeated every 2 weeks. Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met.	S-1/Cisplatin n=334 Participants S-1 plus Cisplatin CDDP was administered intravenously at dose of 60 mg/m2 on day 1 (Korea) or day 8 (Japan), and S-1 were administered 40-60 mg orally twice daily for 21 days (day 1 through day 21), repeated every 5 weeks (rest period can be shorten from 14 days to 7 days). Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met.	Total n=681 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	201 Participants n=5 Participants	194 Participants n=7 Participants	395 Participants n=5 Participants
Age, Categorical >=65 years	146 Participants n=5 Participants	140 Participants n=7 Participants	286 Participants n=5 Participants
Age, Continuous	62.0 years n=5 Participants	62.0 years n=7 Participants	62.0 years n=5 Participants
Sex: Female, Male Female	96 Participants n=5 Participants	116 Participants n=7 Participants	212 Participants n=5 Participants
Sex: Female, Male Male	251 Participants n=5 Participants	218 Participants n=7 Participants	469 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	347 Participants n=5 Participants	334 Participants n=7 Participants	681 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	347 Participants n=5 Participants	334 Participants n=7 Participants	681 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 Japan	221 participants n=5 Participants	212 participants n=7 Participants	433 participants n=5 Participants
Region of Enrollment South Korea	126 participants n=5 Participants	122 participants n=7 Participants	248 participants n=5 Participants

PRIMARY outcome

Timeframe: A survival follow-up was required every 12 weeks from the date of randomization to the date of death from any cause, whichever came first, assessed up to 38 months.

Population: Full Analysis Set (FAS)：Patients in AT population who have advanced gastric cancer at randomization.

Outcome measures

Outcome measures
Measure	TAS-118/Oxaliplatin n=347 Participants TAS-118 plus Oxaliplatin L-OHP was administered intravenously at dose of 85 mg/m2 on day 1, and TAS-118 were administered 30-60 mg orally twice daily for 7 days (day 1 through day 7), repeated every 2 weeks. Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met.	S-1/Cisplatin n=334 Participants S-1 plus Cisplatin CDDP was administered intravenously at dose of 60 mg/m2 on day 1 (Korea) or day 8 (Japan), and S-1 were administered 40-60 mg orally twice daily for 21 days (day 1 through day 21), repeated every 5 weeks (rest period can be shorten from 14 days to 7 days). Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met.
Overall Survival	16.0 Months Interval 13.8 to 18.3	15.1 Months Interval 13.6 to 16.4

SECONDARY outcome

Timeframe: A radiographic imaging examination using CT or MRI was repeated every 6 weeks. Tumor assessments were performed from the date of randomization to the date of disease progression or death from any cause, whichever came first.

Population: FAS

PFS was defined as the time from the date of randomization to the date of disease progression (assessed by each investigator) or death from any cause, whichever came first.

Outcome measures

Outcome measures
Measure	TAS-118/Oxaliplatin n=347 Participants TAS-118 plus Oxaliplatin L-OHP was administered intravenously at dose of 85 mg/m2 on day 1, and TAS-118 were administered 30-60 mg orally twice daily for 7 days (day 1 through day 7), repeated every 2 weeks. Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met.	S-1/Cisplatin n=334 Participants S-1 plus Cisplatin CDDP was administered intravenously at dose of 60 mg/m2 on day 1 (Korea) or day 8 (Japan), and S-1 were administered 40-60 mg orally twice daily for 21 days (day 1 through day 21), repeated every 5 weeks (rest period can be shorten from 14 days to 7 days). Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met.
Progression-free Survival	7.1 Months Interval 6.8 to 8.3	6.4 Months Interval 5.6 to 6.9

SECONDARY outcome

Timeframe: From the date of randomization to the date of the last administration of the study drug.

TTF was defined as the time from the date of randomization to the date of the last administration of the study drug. Patients on study treatment were censored at the date of the last administration or the cutoff date, whichever came earlier.

Outcome measures

Outcome measures
Measure	TAS-118/Oxaliplatin n=347 Participants TAS-118 plus Oxaliplatin L-OHP was administered intravenously at dose of 85 mg/m2 on day 1, and TAS-118 were administered 30-60 mg orally twice daily for 7 days (day 1 through day 7), repeated every 2 weeks. Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met.	S-1/Cisplatin n=334 Participants S-1 plus Cisplatin CDDP was administered intravenously at dose of 60 mg/m2 on day 1 (Korea) or day 8 (Japan), and S-1 were administered 40-60 mg orally twice daily for 21 days (day 1 through day 21), repeated every 5 weeks (rest period can be shorten from 14 days to 7 days). Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met.
Time to Treatment Failure	6.1 Months Interval 5.6 to 6.7	5.3 Months Interval 4.7 to 6.2

SECONDARY outcome

Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 42 months.

Population: Tumor Response (TR) Evaluable Population： Patients in FAS population presenting measurable lesions (at least one target lesion), evaluated for tumor responses at least once during treatment with the study drug.

ORR was defined as the proportion of patients with the best unconfirmed overall response of complete response (CR) or partial response (PR) in patients with measurable lesions

Outcome measures

Outcome measures
Measure	TAS-118/Oxaliplatin n=211 Participants TAS-118 plus Oxaliplatin L-OHP was administered intravenously at dose of 85 mg/m2 on day 1, and TAS-118 were administered 30-60 mg orally twice daily for 7 days (day 1 through day 7), repeated every 2 weeks. Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met.	S-1/Cisplatin n=212 Participants S-1 plus Cisplatin CDDP was administered intravenously at dose of 60 mg/m2 on day 1 (Korea) or day 8 (Japan), and S-1 were administered 40-60 mg orally twice daily for 21 days (day 1 through day 21), repeated every 5 weeks (rest period can be shorten from 14 days to 7 days). Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met.
Overall Response Rate	155 Participants	106 Participants

SECONDARY outcome

Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 42 months.

Population: TR Evaluable Population：

DCR was defined as the proportion of patients with CR, PR, or stable disease in patients with measurable lesions.

Outcome measures

Outcome measures
Measure	TAS-118/Oxaliplatin n=211 Participants TAS-118 plus Oxaliplatin L-OHP was administered intravenously at dose of 85 mg/m2 on day 1, and TAS-118 were administered 30-60 mg orally twice daily for 7 days (day 1 through day 7), repeated every 2 weeks. Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met.	S-1/Cisplatin n=212 Participants S-1 plus Cisplatin CDDP was administered intravenously at dose of 60 mg/m2 on day 1 (Korea) or day 8 (Japan), and S-1 were administered 40-60 mg orally twice daily for 21 days (day 1 through day 21), repeated every 5 weeks (rest period can be shorten from 14 days to 7 days). Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met.
Disease Control Rate	197 Participants	187 Participants

Adverse Events

TAS-118/Oxaliplatin

Serious events: 155 serious events

Other events: 344 other events

Deaths: 22 deaths

S-1/Cisplatin

Serious events: 159 serious events

Other events: 328 other events

Deaths: 8 deaths

Serious adverse events

Other adverse events

Additional Information

Taiho Pharmaceutical Co., Ltd.

Clinical Trial Registration Contact

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	TAS-118/Oxaliplatin n=352 participants at risk TAS-118 plus Oxaliplatin L-OHP was administered intravenously at dose of 85 mg/m2 on day 1, and TAS-118 were administered 30-60 mg orally twice daily for 7 days (day 1 through day 7), repeated every 2 weeks. Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met.	S-1/Cisplatin n=348 participants at risk S-1 plus Cisplatin CDDP was administered intravenously at dose of 60 mg/m2 on day 1 (Korea) or day 8 (Japan), and S-1 were administered 40-60 mg orally twice daily for 21 days (day 1 through day 21), repeated every 5 weeks (rest period can be shorten from 14 days to 7 days). Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met.
Blood and lymphatic system disorders Lymphadenitis	0.00% 0/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.29% 1/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Blood and lymphatic system disorders Anaemia	0.57% 2/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	1.4% 5/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.85% 3/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.00% 0/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Blood and lymphatic system disorders Febrile neutropenia	1.1% 4/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	1.7% 6/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Cardiac disorders Acute myocardial infarction	0.00% 0/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.29% 1/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Cardiac disorders Prinzmetal angina	0.00% 0/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.29% 1/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Eye disorders Rhegmatogenous retinal detachment	0.28% 1/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.00% 0/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Abdominal distension	0.00% 0/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.86% 3/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Abdominal pain	2.8% 10/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	2.6% 9/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Abdominal pain upper	0.28% 1/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.00% 0/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Ascites	1.4% 5/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	2.3% 8/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Cheilitis	0.28% 1/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.00% 0/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Colitis	0.28% 1/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.00% 0/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Diarrhoea	4.0% 14/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	2.3% 8/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Dyspepsia	0.00% 0/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.29% 1/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Dysphagia	0.28% 1/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.29% 1/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Enteritis	1.4% 5/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.57% 2/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Enterocolitis	0.85% 3/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.00% 0/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Gastric haemorrhage	0.85% 3/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.57% 2/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Gastric perforation	0.00% 0/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.86% 3/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.29% 1/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.57% 2/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Gastrointestinal necrosis	0.28% 1/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.00% 0/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Gastrointestinal perforation	0.00% 0/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.29% 1/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Haematemesis	0.28% 1/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.00% 0/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Haematochezia	0.28% 1/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.00% 0/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Ileus	2.0% 7/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	1.4% 5/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Ileus paralytic	0.00% 0/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.29% 1/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Inguinal hernia	0.00% 0/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.29% 1/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Large intestine perforation	0.00% 0/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.29% 1/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Nausea	3.1% 11/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	1.7% 6/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Obstruction gastric	0.85% 3/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	2.3% 8/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Pancreatitis	0.28% 1/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.00% 0/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Rectal stenosis	0.00% 0/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.29% 1/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.86% 3/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Stomatitis	0.00% 0/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.57% 2/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Vomiting	1.1% 4/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.29% 1/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Oesophageal discomfort	0.28% 1/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.00% 0/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.28% 1/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	0.00% 0/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Gastric stenosis	0.57% 2/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	1.1% 4/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.

Other adverse events
Measure	TAS-118/Oxaliplatin n=352 participants at risk TAS-118 plus Oxaliplatin L-OHP was administered intravenously at dose of 85 mg/m2 on day 1, and TAS-118 were administered 30-60 mg orally twice daily for 7 days (day 1 through day 7), repeated every 2 weeks. Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met.	S-1/Cisplatin n=348 participants at risk S-1 plus Cisplatin CDDP was administered intravenously at dose of 60 mg/m2 on day 1 (Korea) or day 8 (Japan), and S-1 were administered 40-60 mg orally twice daily for 21 days (day 1 through day 21), repeated every 5 weeks (rest period can be shorten from 14 days to 7 days). Treatment was continued during the study period unless any of Study Treatment Discontinuation Criteria was met.
Gastrointestinal disorders Diarrhoea	53.7% 189/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	38.5% 134/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Dyspepsia	5.7% 20/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	3.7% 13/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Nausea	56.8% 200/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	53.4% 186/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Stomatitis	42.0% 148/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	25.3% 88/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Vomiting	28.4% 100/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	20.1% 70/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
General disorders Fatigue	33.0% 116/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	30.5% 106/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
General disorders Malaise	21.9% 77/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	21.8% 76/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
General disorders Oedema	2.6% 9/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	7.5% 26/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
General disorders Oedema peripheral	6.0% 21/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	7.8% 27/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
General disorders Pyrexia	12.8% 45/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	9.2% 32/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Investigations Alanine aminotransferase increased	12.8% 45/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	5.7% 20/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Investigations Aspartate aminotransferase increased	14.2% 50/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	5.5% 19/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Investigations Blood creatinine increased	1.7% 6/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	9.5% 33/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Blood and lymphatic system disorders Anaemia	26.7% 94/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	27.6% 96/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Blood and lymphatic system disorders Leukopenia	4.0% 14/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	5.5% 19/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Blood and lymphatic system disorders Neutropenia	14.2% 50/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	15.2% 53/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Eye disorders Lacrimation increased	11.6% 41/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	10.6% 37/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Abdominal pain	13.1% 46/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	8.6% 30/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Gastrointestinal disorders Constipation	22.7% 80/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	25.9% 90/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Investigations Neutrophil count decreased	25.6% 90/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	33.0% 115/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Investigations Platelet count decreased	29.3% 103/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	21.8% 76/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Investigations Weight decreased	22.2% 78/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	11.8% 41/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Investigations White blood cell count decreased	12.8% 45/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	21.8% 76/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Investigations Blood alkaline phosphatase increased	7.7% 27/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	2.9% 10/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Metabolism and nutrition disorders Hypoalbuminaemia	11.4% 40/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	7.2% 25/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Metabolism and nutrition disorders Hypokalaemia	5.4% 19/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	4.0% 14/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Metabolism and nutrition disorders Hyponatraemia	2.0% 7/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	5.5% 19/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Metabolism and nutrition disorders Decreased appetite	66.5% 234/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	62.1% 216/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Nervous system disorders Dizziness	5.1% 18/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	9.8% 34/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Nervous system disorders Dysgeusia	31.8% 112/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	23.6% 82/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Nervous system disorders Neuropathy peripheral	6.0% 21/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	2.0% 7/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Nervous system disorders Peripheral sensory neuropathy	68.8% 242/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	15.5% 54/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Respiratory, thoracic and mediastinal disorders Hiccups	5.4% 19/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	17.8% 62/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Skin and subcutaneous tissue disorders Alopecia	3.1% 11/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	6.6% 23/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	17.0% 60/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	7.8% 27/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Skin and subcutaneous tissue disorders Rash	5.1% 18/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	5.5% 19/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	17.9% 63/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	14.4% 50/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Skin and subcutaneous tissue disorders Pigmentation disorder	9.1% 32/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	4.9% 17/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.
Vascular disorders Vascular pain	9.1% 32/352 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.	2.6% 9/348 • From the time a patient signed informed consent until 30 day safety follow-up visit or initiation of new anticancer treatment, whichever was earlier, an average assessed up to 42 months. An adverse event (AE) is any untoward medical condition that occurs in a patient while participating in a clinical study and does not necessarily have a causal relationship with the use of the product. Treatment emergent adverse events are AEs that occur from the initiation of any study medication administration, and do not necessarily have a causal relationship to the use of the study medication.