S-1 Plus Docetaxel Versus S-1 for Advanced Gastric Cancer (START TRIAL) Update 2012 (JACCRO AND KCSG STUDY GROUP)

ABSTRACT Background S-1, an oral fluoropyrimidine, is used as a standard treatment for advanced and recurrent gastric cancer (AGC) in East Asia. A phase 3 multicenter study was performed in Japan and Korea to evaluate potential benefits of adding docetaxel to S-1 in patients with AGC. Results of this study were reported through planned analysis at ASCO GI 2011 (YH Kim, et al.). However an independent biostatistician pointed out that there was large number of censored cases led to insufficient number of events for proper analysis. According to the recommendations by the statistician, further follow up of survival status was performed to analyze the START trial properly. Methods Patients with unresectable or recurrent gastric cancer were randomly assigned to docetaxel plus S-1 (DS) or S-1 alone (S-1). The DS group received 40 mg/m2 of docetaxel on day 1 intravenously and 80 mg/m2 of S-1 on days 1 to 14 orally of a 21-day cycle. The S-1 group received 80 mg/m2 of S-1 on days 1 to 28 of a 42-day cycle. The primary end point was overall survival (OS) and the secondary endpoints were including progression-free survival (PFS) and response rate (RR). Results Of the 639 patients enrolled, 635 were eligible for analysis. The median survival time was 12.48 months in the DS group and 10.78 months in the S-1 group (p = 0.0319), (HR = 0.837 95% CI: 0.711-0.985). PFS was 5.29 months in the DS group and 4.17 months in the S-1 group (p = 0.001). RR was 38.8% (32.8-45.2) in the DS group and 26.8% (21.6-32.6) in the S-1 group (p = 0.0048). As for adverse events, neutropenia was more frequent in the DS group and one patient died by Grade 4 thrombocytopenia in the DS group. Conclusion Adding docetaxel to S-1 significantly improved OS, PFS and RR, nevertheless resulted in some increasing proportion of haematological toxicities. DS is a new treatment option for patients with untreated AGC. Disclosure K. Yoshida: Research fund from Chugai Pharmaceutical Co. Yakult Honsha, Taiho Phamaceutical Co. All other authors have declared no conflicts of interest.