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Life sciences · Journal article
Frontiers in Immunology · September 17, 2026
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Background Immune checkpoint inhibitors (ICIs) are a cornerstone of therapy for advanced non–small cell lung cancer (NSCLC). Elderly patients remain underrepresented in clinical trials, and the prognostic significance of immune-related adverse events (irAEs)—including their cumulative burden—across age groups is not fully defined. This study evaluated age-related differences in clinical characteristics, treatment patterns, irAEs, and outcomes in patients with stage IV NSCLC. Methods This retrospective multicenter study included 452 patients with metastatic NSCLC treated with ICIs, with or without chemotherapy. Patients were stratified by age (<75 vs. ≥75 years). irAEs were analyzed both by occurrence (yes vs. no) and by burden (≤2 vs. >2 different irAE types). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared across age and irAE subgroups. Results Among the 452 patients, 344 (76.1%) were <75 years old and 108 (23.9%) were of ages ≥75 years. Baseline characteristics, including histology and PD-L1 expression, were comparable between age groups. Older patients were more frequently treated with immunotherapy alone or dual immunotherapy and less often received chemo-immunotherapy (p = 0.024). The distribution of irAEs differed significantly by age (p < 0.001), with patients ≥75 years of age experiencing a higher frequency of >2 irAE types. The median PFS and OS for the entire cohort were 12.0 and 15.0 months, respectively. While PFS was similar between age groups, OS was significantly shorter in patients of age ≥75 years (p = 0.008). Across both age groups, the occurrence of irAEs was associated with significantly improved PFS and OS. A higher irAE burden (>2 different types) was associated with numerically longer survival in both younger and older patients. Conclusions ICIs are effective in elderly patients with advanced NSCLC. The presence of irAEs—and potentially a higher irAE burden—is associated with improved survival outcomes regardless of age, supporting irAEs as a clinically meaningful biomarker of immunotherapy benefit, including in patients ≥75 years of age.