Abstract 412P
Background
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), and the results were opened by the recommendation of JCOG Data and Safety Monitoring Committee (Lancet Gastroenterol Hepatol 2018). We report the 6-year survival updated data to confirm the conclusion at the interim analysis.
Methods
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.
Results
Between March 1, 2010, and Aug 23, 2013, 1,564 patients were randomized to capecitabine (n = 782) or S-1 (n = 782). At the end of the follow-up period of 6 years, 77% of required events (412/535) were observed, with a median follow-up for all randomized patients of 6.1 years, 3- and 6-year DFS was 81.5% (95% CI, 78.6-84.1%) and 77.3% (74.2-80.1%) in capecitabine and 78.3% (75.2-81.0%) and 72.2% (68.9-75.2%) in S-1. The HR of DFS was 1.20 (95% CI, 0.99–1.46). 6-year overall survival (OS) was 91.2% (89.0-93.1%) in capecitabine and 88.4% (85.8-90.5%) in S-1. The HR of OS was 1.31 (95% CI, 0.98–1.75). Six-year relapse-free survival (RFS: relapse, death are events) was 82.1% (79.2-84.6%) in capecitabine and 78.3% (75.2-81.1%) in S-1. The HR of RFS was also 1.21 (95% CI, 0.97–1.51). In the subgroup analyses, no significant interactions were identified between the major baseline characteristics.
Conclusions
This updated analysis has confirmed the conclusion reached in the earlier publication of the second interim analysis. Adjuvant capecitabine remains one of the standard treatments and S-1 is not recommended.
Clinical trial identification
UMIN000003272.
Editorial acknowledgement
Legal entity responsible for the study
Japan Clinical Oncology Group.
Funding
National Cancer Center, and Ministry of Health, Labour and Welfare of Japan.
Disclosure
T. Hamaguchi: Honoraria (self), Research grant/Funding (self): Chugai Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Esisai ; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self): Merck; Honoraria (self): Takeda Pharmaceutical; Honoraria (self): Yakult Pharmaceutical; Honoraria (self): Sanofi; Honoraria (self): Bristol Meyers; Honoraria (self): Lilly; Honoraria (self): Bayer; Honoraria (self): Fuji Film. J. Mizusawa: Honoraria (self): Chugai pharmaceutical. J. Watanabe: Honoraria (self): Johnson and Johnson; Honoraria (self): Medtronic. T. Kato: Honoraria (self): Chugai pharmaceutical; Honoraria (self): Taiho pharmaceutical. H. Fukuda: Honoraria (self): Chugai pharmaceutical. All other authors have declared no conflicts of interest.