Hironaka 2016.

Methods	Multicentre, randomised, open‐label, 3‐armed, phase 2 trial
Participants	Median (IQR) age in the 3 arms was 65 (60–70), 65 (58–71), 65 (59–69) years
Interventions	S‐1 plus leucovorin (S‐1 40–60 mg orally plus oral leucovorin 25 mg twice a day for 1 week, every 2 weeks), S‐1 plus leucovorin and oxaliplatin (S‐1 plus leucovorin and intravenous oxaliplatin 85 mg/m2 on day 1, every 2 weeks), or S‐1 plus cisplatin (S‐1 40–60 mg orally twice a day for 3 weeks, plus intravenous cisplatin 60 mg/m2 on day 8, every 5 weeks) 49 patients were randomly assigned to the S‐1 plus leucovorin group, 47 to the S‐1 plus leucovorin and oxaliplatin group, and 49 to the S‐1 plus cisplatin group
Outcomes	Primary endpoint was overall response as assessed by an independent review committee, defined as a confirmed complete response or partial response. Secondary endpoints were overall survival, progression‐free survival, time to treatment failure, disease control, duration of response, and toxic effects
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was done centrally with the minimisation method using performance status (0 vs 1) and tumour stage (stage IV vs recurrent) as stratification factors
Allocation concealment (selection bias)	Low risk	Randomisation sequence was generated by EPS Corporation (Tokyo, Japan) independently from the study sponsor
Incomplete outcome data (attrition bias) efficacy	Low risk	After randomisation, one patient did not receive treatment because of aspiration pneumonia. †Two patients who were judged to have no measurable lesions by the independent review committee after enrolment were excluded from the efficacy analyses
Incomplete outcome data (attrition bias) safety	Low risk	After randomisation, one patient did not receive treatment because of aspiration pneumonia. †Two patients who were judged to have no measurable lesions by the independent review committee after enrolment were excluded from the efficacy analyses
Selective reporting (reporting bias)	Low risk	All prespecified outcomes were reported
Other bias	Unclear risk	N/A
Blinded review of CT/MRI‐scans?	Low risk	independent data monitoring committee (but not stated review committee was blinded)