We demonstrated that the second planned interim analysis (median follow-up, 23.7 months) of the JCOG0910 failed to show non-inferiority of adjuvant S-1 to capecitabine in disease-free survival (DFS: relapse, second malignancy, death are events) at ASCO2015 (abstract # 3512), and the results were opened by the recommendation of JCOG Data and Safety Monitoring Committee. We updated the follow-up data to confirm the conclusion at the interim analysis.
Key eligibility criteria were: stage III, colorectal adenocarcinoma except for lower rectal cancer, R0 with D2/3 lymph node dissection. Patients were randomized to 8 courses of capecitabine (1,250 mg/m2 twice daily, days 1–14, every 3 weeks) or 4 courses of S-1 (40 mg/m2 twice daily, days 1–28, every 6 weeks). Primary endpoint was DFS. Planned sample size was 1,550 in order to provide 80% power with a non-inferiority margin at a hazard ratio (HR) of 1.24 and 1-sided α = 0.05. This trial is registered with UMIN-CTR, #UMIN000003272.
1,564 patients were randomized to capecitabine (n = 782) or S-1 (n = 782). At the end of the follow-up period of 3 years, 69% of required events (368/535) were observed, with a median follow-up for all randomized patients of 4.13 years, 3-year DFS was 81.7% (95% CI, 78.8 - 84.2%) in capecitabine and 78.3% (75.2 - 81.0%) in S-1. The HR of DFS was 1.22 (95% CI, 1.00–1.50) and the non-inferiority of S-1 was not demonstrated (P for non-inferiority = 0.448). Three-year relapse-free survival (RFS: relapse, death are events) was 84.6% in capecitabine and 81.5% in S-1. The HR of RFS was also 1.21 (95% CI, 0.96–1.53). Three-year overall survival (OS) was 96.3% in capecitabine and 95.4% in S-1. The HR of OS was 1.18 (95% CI, 0.83–1.68). In the subgroup analyses, no significant interactions were identified between the major baseline characteristics.
These updated results confirmed that S-1 could not be demonstrated to be non-inferior to capecitabine in DFS. Adjuvant capecitabine remains the standard treatment and S-1 is not recommended.
Clinical trial identification
Legal entity responsible for the study
Japan Clinical Oncology Group
National Cancer Center and Ministry of Health, Labour and Welfare of Japan
T. Hamaguchi: Honoraria from Chugai, Merck Serono, Takeda, Yakult, and Taiho. Reserach funding (to institute) from Dainippon Sumitomo, Sanofi, NanoCarrier, Taiho, Ono, Daiichi Sankyo, Teijin, and MSD. Advisory role for NanoCarrier. Y. Shimada: Research funding (to institute) from Taiho, Ili Lilly, Merck Serono, and MSD. Honoraria from Taiho, Chugai, Ili Lilly, Ono, Novartis, Bayer, and Merck Serono. T. Kato: Honoraria from Chugai, Takeda, Eli Lilly, Bayer, Sanofi, and Yakult. K. Sugihara: Research fundings (to institute) from Chugai, Taiho, and Takeda. Honoraria from Chugai, Taiho, Yakult, Merck Serono, Bristol-Myers Squibb, and Takeda. Y. Saida: Honoraria from Chugai, Taiho, Merck Serorno, and Takeda. Research funding (to institute) from Chugai, Taiho, Yakult and Takeda. T. Masaki: Honoraria from Chugai, Taiho, Yakult, and Kyorin Pharmaceutical Campany. K. Nakamura: Honorarium from Taiho. H. Fukuda: Honoraria from Taiho and Chugai. All other authors have declared no conflicts of interest.