762PA randomized phase II trial of adjuvant chemotherapy with gemcitabine versus S-1 after major hepatectomy for biliary tract cancer: Kansai Hepato-Biliary Oncology Group (KHBO1208)

Background: No adjuvant chemotherapy regimens after major hepatectomy for biliary tract cancer (BTC) have been standardized due to the frequency of adverse events. Survival benefits of adjuvant gemcitabine (GEM) or S-1 (S1) chemotherapy were investigated with the recommended dose determined in our previous clinical trial (KHBO1003), with 10% dose-limited toxicity. Methods: We performed a phase II multicenter randomized trial. The primary end-point was 1-year recurrence-free survival (RFS), and the secondary end-points were other RFS, overall survival (OS), and others. The following 6-month adjuvant chemotherapy regimens were performed within 12 weeks after R0 or R1 major hepatectomy (hemihepatectomy or trisectionectomy) for BTC: GEM (1000 mg/m2) every 2 weeks or S1 (80 mg/m2/day) for 28 days every 6 weeks. Thirty-five patients were assigned to each arm (alpha error, 10%; beta error, 20%). P values of < 0.10 were considered to indicate a statistically significant difference. Results: No patients were excluded for the per-protocol analysis. There were no statistically significant differences in the patient characteristics of the two arms. The 1-year RFS and the 1-year OS rates of the GEM arm were 51.4% and 80.0%, respectively, while those of the S1 arm were 62.9% and 97.1%, respectively. The 2-year RFS rate, the 1- and 2-year OS rates, and the OS curve of the S1 arm were superior to those of the GEM arm (p = 0.0894, p = 0.0242, p = 0.0679, and p = 0.0606, respectively), although the 1-year RFS rate was not significantly different (p = 0.334). With regard to the OS curve, the hazard ratio of the S1 group was 0.477 (90% confidence interval, 0.245-0.927). Conclusions: The adjuvant chemotherapy with S1 may provide better survival benefits compared with that with GEM after major hepatectomy for BTC. Clinical trial identification: NCT01815307 (March 21, 2013). Legal entity responsible for the study: Kansai Hepato-Biliary Oncology Group. Funding: Japan Society of Clinical Oncology Clinical Research Grant Program 2012 and 2013. Disclosure: I. Ikai, S. Morita: Lecture fee: Taiho Pharmaceutical Co., Eli Lilly Japan K.K. T. Ioka: Research funding, Lecture fee: Taiho Pharmaceutical Co. All other authors have declared no conflicts of interest.