Seasonal influences on the efficacy of anti–programmed cell death (ligand) 1 inhibitors in lung cancer

• Published in: Cancer 2024-11, Vol.130 (21), p.3647-3657
• Main Authors: Cho, Hyunsoon, Kwon, Hoejun, Kim, Se Hyun, Ahn, Hyung‐Min, Choi, Beom K., Lee, Geon Kook, Park, Seog‐Yun, Lim, Hyun‐ju, Hwang, Jung‐Ah, Lim, Jiyeon, Han, Ji‐Youn, Lee, Youngjoo
• Format: Article
• Language: English
• Subjects: Aged; anti–programmed cell death (ligand) 1 (anti–PD‐[L]1) inhibitor; Apoptosis; B7-H1 Antigen - antagonists & inhibitors; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Cell death; Effectiveness; Female; Humans; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Impact analysis; Inhibitors; Kaplan-Meier Estimate; Ligands; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Middle Aged; Mortality; Non-small cell lung carcinoma; prognosis; Progression-Free Survival; Prospective Studies; Seasonal variations; seasonality; Seasons; Small cell lung carcinoma; Statistical models; Subgroups; Survival; systemic immunity; Treatment Outcome; Winter
• ISSN: 0008-543X; 1097-0142; 1097-0142
• DOI: 10.1002/cncr.35454

Background Seasonal variations in systemic immunity have been reported. This study aimed to evaluate whether seasonality affects the efficacy of anticancer immunotherapy. Methods A total of 604 patients with lung cancer receiving single anti–programmed cell death (ligand) 1 (anti–PD‐[L]1) inhibitors from two prospective observational cohorts were screened. Primary outcomes were progression‐free survival (PFS) and overall survival (OS). Patients were classified into two groups according to the season when the treatment started: winter (November–February) and other seasons (March–October). Kaplan–Meier analysis and Cox proportional hazards models were fitted to evaluate the impact of seasonality on survival. For validation, propensity score matching was performed. Results A total of 484 patients with advanced non–small cell lung cancer were included. In an unmatched population, multivariable analysis demonstrated that the winter group (n = 173) had a significantly lower risk of progression or death from immunotherapy than the other group (n = 311) (PFS: hazard ratio [HR], 0.77 [95% confidence interval (CI), 0.62–0.96]; p = .018; OS: HR, 0.77 [95% CI, 0.1–0.98]; p = .032). In a propensity score–matched population, the winter group (n = 162) showed significantly longer median PFS (2.8 months [95% CI, 1.9–4.1 months] vs. 2.0 months [95% CI, 1.4–2.7 months]; p = .009) than the other group (n = 162). The winter group’s median OS was also significantly longer than that of the other group (13.4 months [95% CI, 10.2–18.0 months] vs. 8.0 months [95% CI, 3.6–8.7 months]; p = .012). The trend toward longer survival in the winter group continued in subgroup analyses. Conclusions Starting an anti–PD‐(L)1 inhibitor in winter was associated with better treatment outcomes in patients with lung cancer compared to other seasons. Patients with lung cancer who started anti–programmed cell death (ligand) 1 inhibitor treatment in the winter season from November to February showed significantly better survival outcomes than those who started treatment in the other seasons. This observation was validated in further analysis via propensity score matching.