Randomized phase III study of gemcitabine plus S-1 (GS) versus S-1 versus gemcitabine (GEM) in unresectable advanced pancreatic cancer (PC) in Japan and Taiwan: GEST study

4007 Background: S-1, an oral fluoropyrimidine, is one of the key drugs for PC in Japan. Phase II studies of S-1 alone as well as those of GS have shown high efficacy against the tumor as the first-line treatment of metastatic PC. Methods: The GEST study was a randomized, prospective, open-label, 3-arm, phase III study. Chemotherapy-naive patients with unresectable advanced PC, an ECOG PS of 0-1, with adequate organ functions were randomly assigned to receive GEM (1000 mg/m2, iv, d1, 8 and 15, q4w), S-1 (80/100/120 mg/day based on BSA, po, d1-28, q6w) or GS (GEM 1000 mg/m2, iv, d1 and 8 plus S-1 60/80/100 mg/day based on BSA po, d1-14, q3w). The primary endpoint was overall survival (OS) to assess the non-inferiority of S-1 alone and the superiority of GS to GEM, with a 90% power and a 1-sided alpha value of 0.0125 for each multiplicity-adjusted comparison. Secondary endpoints were progression-free survival (PFS), response rate (RR), safety, and quality of life (EQ-5D). Results: A total of 834 patients we...