Effect of immune checkpoint inhibitor infusion timing on overall survival in non–small cell lung cancer: A real-world retrospective study.

Abstract

e20595 Background: Circadian regulation of immune function has been proposed as a modifier of immune checkpoint inhibitor (ICI) efficacy, with retrospective studies suggesting improved outcomes with earlier infusion timing. Whether these findings translate to routine oncology practice, where ICIs are administered across multiple lines, frequently combined with chemotherapy, and subject to treatment interruptions, remains uncertain. We evaluated the association between ICI infusion timing and overall survival (OS) in a real-world cohort of patients with non-small cell lung cancer (NSCLC). Methods: A retrospective cohort study included adults with NSCLC who received at least one line of ICI therapy at a community oncology center between January 2018 and December 2024. Infusion timing was defined at the patient level as morning-only ( < 1300 hours), evening-only (≥1300 hours), or mixed timing, reflecting receipt of infusions exclusively in different time-of-day categories across treatment lines. OS was measured from diagnosis to death or last follow-up. Kaplan-Meier and Cox proportional hazards models were used. Multivariable analyses adjusted for stage, ECOG performance status, body mass index, and premature ICI discontinuation. Line of therapy was excluded due to collinearity with mixed-timing classification and risk of immortal time bias. Results: A total of 127 patients were included (morning-only n = 77; mixed timing n = 36; evening-only n = 14). Staging data were available for 99.2%, and 94 deaths occurred. Median OS was 495 days for morning-only, 850 days for mixed timing, and 388 days for evening-only patients. Kaplan-Meier analysis showed no statistically significant OS differences across groups. In sensitivity analysis excluding patients with mixed infusion timing, morning-only and evening-only groups demonstrated overlapping survival curves, with no evidence of a time-of-day–specific survival advantage. In univariate analysis, mixed timing was associated with a borderline reduction in mortality compared with morning-only infusions (HR 0.63, 95% CI 0.39-1.00), while evening-only timing was not (HR 1.63, 95% CI 0.85-3.16). In multivariate analysis restricted to stage III-IV disease, infusion timing was not independently associated with OS. ECOG performance status, premature ICI discontinuation and advanced staging were the strongest predictors of mortality. Conclusions: In this real-world NSCLC cohort, ICI infusion timing was not independently associated with overall survival after adjustment for patient fitness and treatment continuity. These findings suggest that in pragmatic settings, clinical factors may outweigh subtle chronotherapy effects reported in more selected populations.