Initiation of immune checkpoint inhibitor therapy in winter is associated with improved overall survival in patients with advanced non-small cell lung cancer
Abstract
Immune checkpoint inhibitors (ICIs), targeting programmed cell death protein 1, programmed death-ligand 1 and cytotoxic T-lymphocyte-associated protein 4, have become a standard treatment resulting in improved outcomes in advanced non-small cell lung cancer (NSCLC); however, the influence of seasonal variations on treatment efficacy and toxicity remains underexplored. In the present single-center retrospective study, 310 patients with advanced NSCLC who initiated first-line ICI therapy between January 2018, and December 2023 were analyzed. Patients were categorized by season of treatment initiation: Winter (December-February), spring (March-May), summer (June-August) and autumn (September-November). Primary endpoints were overall survival (OS) and progression-free survival (PFS), assessed via Kaplan-Meier and Cox regression analyses. Immune-related adverse events (irAEs) were evaluated using χ2 tests. Winter initiation of ICI was associated with the most favorable OS (P=0.02) but no significant difference in PFS was observed across seasonal groups (P=0.74). After multivariable adjustment, winter initiation remained an independent prognostic factor for OS, with adjusted hazard ratios of 1.82 (95% CI: 0.88–3.77; P=0.105) for summer and 2.59 (95% CI: 1.37–4.87; P=0.003) for spring/autumn, using winter as reference. The overall incidence of irAEs did not differ by season; however, respiratory irAEs, predominantly immune-mediated pneumonitis, were significantly more frequent in patients initiating ICI in winter (17.1%) compared with summer (5.9%; adjusted P=0.026). In conclusion, initiation of ICI therapy during winter is associated with improved overall survival in advanced NSCLC but may also confer a higher risk of immune-mediated pneumonitis. These findings highlight the potential role of seasonal factors in optimizing immunotherapy timing and monitoring.