Statistical analyses
EVENTS, SECONDARY
An estimated sample size of 780 patients (520 patients in the nivolumab group and 260 patients in the placebo group) was planned to achieve the required 154 RFS events to detect a statistically significant difference between the treatment arms at final analysis with ≥90% statistical power if the average HR of nivolumab versus placebo was 0.573, with a two-sided alpha of 0.05 by a stratified log-rank test. Per protocol, the current pre-specified interim analysis was scheduled to be conducted when approximately 123 RFS events (80% information fraction) had occurred among all randomized patients; a critical HR ≤0.65 would indicate significant improvement with nivolumab versus placebo with ≥62.8% statistical power. The stopping boundaries for both interim and final analyses were derived using the Lan–DeMets alpha spending function with O’Brien–Fleming boundaries. A total of 790 patients were randomized, and, at the data cutoff date of 28 June 2022, there were 135 reported RFS events (88% information fraction), resulting in a critical HR of 0.678 and 76.8% statistical power to detect a difference of RFS between the arms. DMFS was a descriptive secondary endpoint, and the trial was not powered to compare this endpoint between the two treatment groups.A two-sided log-rank test stratified by AJCC 8th edition T category was used to compare the treatments for the intention-to-treat populations for both RFS and DMFS. HRs and CIs were estimated using a stratified Cox proportional hazards model with treatment group as a covariate. Comparison for subgroups was estimated using an unstratified Cox proportional hazards model. Survival was estimated using the Kaplan–Meier product-limit method. Medians and rates were estimated, and corresponding 95% CIs were computed based on a log–log-transformed CI for the survivor function.The efficacy analysis endpoints included all randomized patients (defined as, the intention-to-treat population). Safety was assessed in patients who received at least one dose of study drug.