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Background: Adjuvant chemotherapy with gemcitabine(G)has been standard treatment for resected pancreatic cancer(PC).In the GEST study,S-1(S)had shown non-inferiority to G in overall survival(OS)for unresectable PC.The aim of this phase Ⅲ study is to investigate non-inferiority of S to G on OS as adjuvant chemotherapy for resected PC.Methods: Patients(pts)after macroscopically curative resection of PC with an ECOG PS of 0-1 and adequate organ functions were randomly assigned to G(1000 mg/m2,iv,d1,8 and 15,q4w,for 6 courses)or S(80/100/120 mg/day based on BSA,po,d1-28,q6w,for 4 courses)with balancing by surgical margins(R),nodal status(N)and institution.Primary endpoint was OS.With 180 pts per arm,the study had 80%power to prove non-inferiority with a margin of hazard ratio(HR)1.25 on the basis of expected HR 0.87,with 0.05 two-sided alpha.Secondary endpoints were relapse-free survival(RFS),safety,and quality of life(EQ-5D).One interim analysis was planned after 180 deaths.Results: From 4/2007 to 6/2010,385 pts were enrolled from 33 hospitals in Japan.378 pts(G/S: 191/187)were included in the full analysis set.Pts characteristics(G/S)were well balanced(PS0: 67%/70%,R0: 86%/88%,N0: 38%/36%).Based on the interim analysis with 205 OS events,IDMC recommended to publish the results.OS at 2-years were 53%for G and 70%for S.HR for S to G was 0.56(95%CI,0.42-0.74,p<0.0001 for non-inferiority,p<0.0001 for superiority).On subgroup analysis,HRs for R0/R1,N0/N1 pts were 0.57(95%CI,0.42-0.78)/0.53(0.27-1.05),0.48(0.28-0.83)/0.58(0.41-0.80),respectively.RFS at 2-years were 29%for G and 49%for S.HR of relapse for S to G was 0.56(95%CI,0.43-0.71,log-rank p<0.0001).Incidences of grade 3/4 toxicities in G/S were leukopenia 39%/9%,hemoglobin decrease 17%/13%,thrombocytopenia 9%/4%,elevated AST 5%/1%,fatigue 5%/5%,and anorexia 6%/8%.Relative dose intensity of G/S was 84%/97%.EQ-5D QOL score in S was significantly better than that in G(p<0.0001).Conclusions: S-1 adjuvant chemotherapy is shown non-inferior,and furthermore,even superior to GEM.S-1 is considered as the new standard treatment for resected PC pts.