Koizumi 2014.

Methods	Multicentre RCT 2 arms Quality score: D The study was conducted in Japan and Korea.
Participants	n = 639, 635 eligible (ITT) Median age: 65 years Advanced disease: 83%, relapse: 17% ECOG 2‐3: 0%
Interventions	S‐1+docetaxel: docetaxel (40mg/m2 d1) + S‐1 (40‐60mg/m2 ‐according to BSA‐ twice daily d 1‐14), repeated at d 21 versus S‐1: S‐1 (40‐60mg/m2 ‐according to BSA‐ twice daily d 1‐28), repeated at d 42
Outcomes	Overall survival, progression‐free survival, response rate, safety
Notes	The study was conducted in Japan and Korea. The dose of S‐1 which was used in this trial may not be valid for non‐Asian populations for this reason. This study was registered (NCT00287768).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not stated
Allocation concealment (selection bias)	Unclear risk	Not stated
Incomplete outcome data (attrition bias) efficacy	Low risk	4 (0.6%) patients were ineligible (no measurable or non‐measurable lesions)
Incomplete outcome data (attrition bias) safety	Low risk	All treated patients were included (98%)
Selective reporting (reporting bias)	Low risk	Report includes all expected outcomes
Other bias	High risk	Second‐line treatment was given to 69.7% of patients in the S‐1+docetaxel group and 76% in the S‐1 group, planned interim analysis
Blinded review of CT/MRI‐scans?	Unclear risk	Images were reviewed by a central review board.