Real-world clinical outcomes of immune checkpoint inhibitors beyond 2 Years in patients with non-small cell lung cancer: A multicenter retrospective study

Background Immune checkpoint inhibitors (ICIs) are the standard of care for advanced non-small cell lung cancer (NSCLC). Accumulating clinical evidence, along with increasing consideration of safety and medical costs, has led to growing discussion regarding treatment discontinuation at around 2 years in patients with durable disease control. However, opportunities to evaluate long-term outcomes in patients who continue ICI therapy beyond 2 years are increasingly limited. Methods This multicenter retrospective study included patients with advanced NSCLC treated with ICI for ≥ 25 months at 17 hospitals in Ibaraki Prefecture, Japan, between December 2015 and May 2025. The primary endpoint was progression-free survival (PFS) from the 24-month landmark. Secondary endpoints included overall survival (OS), clinical characteristics, 1-year recurrence-free survival (RFS) after discontinuation, late-onset immune-related adverse events (irAEs), reasons for ICI discontinuation, and outcomes of ICI rechallenge. Results A total of 158 patients were analyzed. The median age was 69 years; 81% were male, 58% had adenocarcinoma, and 88% had Eastern Cooperative Oncology Group performance status 0–1. From the 24-month landmark, PFS rates were 85.6% at 1 year, 80.7% at 2 years, 78.5% at 3 years, and 62.4% at 5 years. Corresponding OS rates were 97.9%, 93.8%, 89.2%, and 77.1%, respectively. The median landmark PFS was 83.6 months; OS was not reached. A total of 24 late-onset irAEs were recorded after ≥ 2 years, with pulmonary events comprising 29.2%. Conclusion In Japanese patients with NSCLC treated with ICIs for more than 2 years, landmark PFS was 83.6 months and OS was not reached, indicating durable outcomes.