Benefit-risk balance of S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC).

backgroundGiven the superior relapse-free survival (RFS) and different safety profiles of 1 year of adjuvant S-1 or uracil/tegafur (UFT) for stage II/III rectal cancer, the benefit-risk of these 2 regimens was formally assessed using the net treatment benefit (NTB). PATIENTS AND

methodsIndividual patient data from the Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC) 35-C1 trial were used. S-1 and UFT were compared regarding RFS, incidence of grade ≥3 symptoms, and incidence of grade ≥3 laboratory abnormalities reported as adverse events (AEs). Laboratory abnormalities and symptoms were analyzed as binary variables and as counts. Univariate and multivariate NTBs were computed for various ways of prioritizing the outcomes.

resultsThe univariate NTB for RFS was 9.2% (95% CI, 3.4%-15.2%, P = .005) in favor of S-1. The univariate NTB was not statistically significant for any symptom. For grade ≥3 laboratory AEs, only thrombocytopenia was statistically significant in favor of UFT (NTB = -0.8%; 95% CI, -1.6% to -0.02%; P = .044). In the multivariate analysis considering RFS as the outcome of first priority, the incidence of grade ≥3 symptoms as second, and the incidence of grade ≥3 laboratory abnormalities as third, the multivariate NTB was 8.8% (95% CI, 2.7%-14.9%, P = .014) in favor of S-1. In sensitivity analyses according to age group, the NTB was generally positive for patients <70 years but nonsignificant for those ≥70 years old.

conclusionThe reanalysis of the JFMC 35-C1 trial suggests that S-1 has a superior benefit-risk to UFT when RFS is considered as the outcome of first priority, followed by the incidence of grade ≥3 symptoms and of grade ≥3 laboratory abnormalities.