799P - The relationship between the survival and fixed dosing of S-1 in advanced gastric cancer patients by pooled analysis using individual data from four Japanese randomized phase III trials

Abstract

BackgroundS-1 is a commonly used agent in first line therapy of advanced gastric cancer in Japan. The recommended initial dose of S-1 is 120mg/day for patients (pts) with a body surface area (BSA) of≥1.5 m2 in Japan. Systemic exposure to 5-FU is significantly lower in Japanese cancer pts with a large BSA of≥1.75 m2 who received the recommended fixed dose of S-1, as compared with those with a BSA of≥1.50 m2 and <1.75 m2 (Ann Oncol 20: 946-949, 2009). However, there has been little knowledge of the relationship between survival and fixed dosing of S-1 in pts with large BSA. MethodsActual data from four randomized Japanese Phase III trials [START (S-1 vs S-1/docetaxel), SPIRITS (S-1 vs S-1/cisplatin), GC0301/TOP-002 (S-1 vs S-1/irinotecan), G-SOX (S-1+cisplatin vs S-1/oxaliplatin)] were combined to evaluate the effect of BSA on survival (OS) in terms of S-1 monotherapy and S-1 combination therapy. The pts were divided into two categories: those with BSA of≥1.50 m2 and <1.75 m2 and those with a BSA of≥1.75m2. The prognostic relevance of BSA was assessed using a multivariate proportional hazards model adjusted for the established clinical prognostic factors including age, performance status, tumor status, primary tumor, hematogenous metastasis, and peritoneal metastasis. ResultsA total of 1,246 pts were available in this analysis (S-1 monotherapy, n=395; S-1 combination therapy, n=851). The median OS for S-1 monotherapy and S-1 combination therapy was 11.7 and 13.6 months, respectively. In pts treated with S-1 monotherapy, OS was significantly shorter in those with a BSA of≥1.75 m2, compared with those with a BSA of≥1.5 m2 and <1.75m2 (HR 1.39; 95% CI 1.05-1.84; p=0.02). However, OS was comparable in the two BSA categories for pts treated with S-1 combination (HR 1.09; 95% CI 0.90-1.34; p=0.349). BSA was an independent prognostic factor in S-1 monotherapy (HR 1.33; 95% CI 0.999-1.77; p=0.05) but not in S-1 combination therapy (HR 1.05; 95% CI 0.85-1.29; p=0.65). ConclusionsAlthough the fixed dosing of S-1 monotherapy affects the survival in pts with large BSA, combination therapy might overcome the worse prognosis even in those with large BSA. Clinical trial identificationUMIN000019519. Legal entity responsible for the studyJapan Clinical Cancer Research Organization. FundingHas not received any funding. DisclosureW. Ichikawa: Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical Co. Ltd.; Honoraria (institution): Takeda Pharmaceutical Co.; Honoraria (self), Research grant / Funding (institution): Merck Serono; Honoraria (self): Bayer Yakuhin Ltd.; Research grant / Funding (institution): Ono Pharmaceutical Co. Ltd.; Research grant / Funding (institution): Shionogi Pharmaceutical Co. Ltd. Y. Sunakawa: Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Honoraria (institution): Taiho Pharmaceutical Co. Ltd; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Yakult Honsha Co. Ltd.; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Merck Serono; Honoraria (self): Bayer Yakuhin Ltd; Honoraria (self), Research grant / Funding (institution): Sanofi K.K.; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan; Research grant / Funding (institution): Daiichi Sankyo Pharmaceutical Co. Ltd.; Research grant / Funding (institution): MSD K.K.; Research grant / Funding (institution): Dainippon Sumitomo Pharmaceutical Co. Ltd.; Research grant / Funding (institution): Solasia Pharma K.K. K. Shitara: Honoraria (self): Novartis; Honoraria (self): AbbVie; Honoraria (self): Yakult; Honoraria (institution), Advisory / Consultancy: Astellas Pharma; Honoraria (institution), Advisory / Consultancy: Lilly; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Takeda; Advisory / Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: Ono Pharmaceutical; Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (institution): Dainippon Sumitomo Pharma; Honoraria (institution): Daiichi Sankyo; Honoraria (institution): Taiho Pharmaceutical; Honoraria (institution): Chugai Pharma; Honoraria (institution): Medi Science. K. Oba: Honoraria (self): Eisai Co., Ltd.; Honoraria (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self): Daiichi-Sankyo Pharmaceutical Co., Ltd.; Honoraria (self): Asahi Kasei Pharma Corp.; Advisory / Consultancy: Takeda Pharmaceuticals, Co., Ltd.; Advisory / Consultancy: Ono Pharmaceutical Co., Ltd. Y. Yamada: Honoraria (self): Taiho Pharmaceutical Co. Ltd.; Honoraria (self): Chugai Pharmaceutical Co. Ltd.; Honoraria (self): Nippon Kayaku; Honoraria (self): Eli Lilly; Honoraria (self): Ono Pharmaceutical Co. Ltd.; Honoraria (self): Bristol-Myers Squibb; Research grant / Funding (institution): Daiichi-Sankyo. Y. Sakata: Honoraria (self): Taiho Pharmaceutical Co. Ltd.; Advisory / Consultancy: Yakult Honsha. M. Takeuchi: Advisory / Consultancy: Hisamitsu Pharmaceutical; Advisory / Consultancy: Kowa; Advisory / Consultancy: Shionogi; Advisory / Consultancy: AbbVie. M. Fujii: Travel / Accommodation / Expenses: Taiho Pharmaceutical Co. Ltd.; Travel / Accommodation / Expenses: Japan Clinical Cancer Research Organization. All other authors have declared no conflicts of interest.