Impact of immunotherapy infusion timing on overall and progression-free survival in advanced NSCLC.

Abstract

e20573 Background: Circadian rhythms regulate immune function through central and peripheral molecular clocks, modulating T-cell activity, antigen presentation, and cytokine release in a time-dependent manner. Preclinical models and retrospective studies suggest that morning hours may represent a period of enhanced antitumor immune responsiveness. However, despite several retrospective analyses evaluating the impact of immunotherapy infusion timing, further investigation is needed to clarify its clinical relevance specifically in lung cancer, particularly in patients with stage IV NSCLC. Therefore, the aim of the present study is to evaluate the association between immunotherapy infusion timing and clinical outcomes, including overall survival and progression-free survival. Methods: We conducted a retrospective cohort study including patients with stage IV NSCLC treated with immune checkpoint inhibitors (ICIs) between 2016 and 2025 in the Instituto Oncologico de Cordoba (IONC). Patients were classified according to infusion timing: before 12:00 (AM group) or after 12:00 (PM group). Clinical characteristics, tumor PD-L1 status, and concomitant treatments were collected. Kaplan–Meier estimates were used for survival analysis. Multivariate Cox regression models adjusted for relevant clinical and biological covariates were performed. Results: Fifty-nine patients were included (AM: n=24; PM: n=35). ORR was higher in the AM group (50% vs. 37.1%), as was the proportion of long-term survivors (87.5% vs. 45.7%). Median PFS was 9.5 months in the AM group vs. 4.3 months in the PM group (p=0.01). Median OS was 21.3 vs. 11.8 months, respectively (p=0.01). After adjustment, morning infusion remained independently associated with lower risk of progression (HR 0.38; 95%CI 0.19–0.79; p=0.01) and death (HR 0.48; 95%CI 0.24–0.98; p=0.04). Conclusions: Our findings suggest that the timing of immunotherapy administration may impact clinical outcomes in patients with advanced NSCLC. Morning administration was associated with improved survival and treatment response. As this is a low-cost, modifiable variable, it deserves further investigation in prospective clinical trials aimed at optimizing treatment efficacy through chronomodulated immuno-oncology strategies.