Time to benefit of perioperative immunotherapy among patients with resectable non-small-cell lung cancer

Abstract

Abstract Background The optimal duration of perioperative immunotherapy for resectable non–small-cell lung cancer (NSCLC) remains undefined, and conventional efficacy measures provide limited insight into the temporal pattern of benefit emergence, for which time-to-benefit (TTB) serves as a complementary metric that quantifies how therapeutic effects accumulate over time and bridges the gap between treatment duration and clinical benefit. This study aimed to quantitatively assess the TTB of perioperative immunotherapy and determine the treatment duration required to achieve predefined absolute risk reduction (ARR) thresholds. Methods This comparative effectiveness study reconstructed individual patient data from eight randomized controlled trials (RCTs) using digitized Kaplan-Meier curves. Pooled survival analyses and Weibull survival modeling with Monte Carlo simulation were applied to estimate TTB at ARR thresholds. Subgroup analyses were conducted by histology, stage, and PD-L1 expression. Results Among 5,123 participants, the entire perioperative immunotherapy significantly improved event-free survival (EFS) and overall survival (OS). TTB analysis showed a near-linear accumulation of benefit: 1.02 months of therapy were required for a 1% EFS-related risk reduction and 9.01 months for a 10% reduction. For OS, a 1% mortality risk reduction required 10.67 months. Subgroup analyses demonstrated that, for the same ARR thresholds, patients with squamous histology, stage III disease, or PD-L1 expression ≥ 1% achieved shorter TTB. Conclusions This study quantitatively evaluated TTB in perioperative immunotherapy for resectable NSCLC, revealing a near-linear accumulation of benefit with meaningful efficacy by 9–10 months, and establishing TTB as a complementary endpoint to guide evidence-based, individualized treatment duration optimization.