Timing of first pembrolizumab infusion and long-term outcomes in non-small cell lung cancer: A retrospective multicenter study. (2025)

[BACKGROUND] Circadian rhythms modulate immunity, and a preclinical study suggests that the timing of the first immune checkpoint inhibitor dose affects antitumor efficacy. However, clinical confirmation is scarce. We aimed to evaluate whether the timing of the first pembrolizumab infusion affects outcomes in unresectable non-small cell lung cancer (NSCLC).

[METHODS] We retrospectively analyzed patients receiving first-line pembrolizumab monotherapy for unresectable NSCLC between 2017 and 2022 at nine Japanese hospitals. Patients were categorized according to the start of first infusion: early (≤ 11:00 AM) or late (> 11:00 AM). A landmark cohort receiving ≥ 4 cycles was balanced on 14 covariates using propensity score matching. Endpoints were overall survival (OS), progression-free surviv