Survival Outcomes After irAE-Related Nivolumab Discontinuation in mNSCLC: A Multicenter Study

Background: Immune checkpoint inhibitors (ICIs) such as nivolumab have transformed the treatment landscape of metastatic non-small cell lung cancer (NSCLC). We aimed to evaluate survival outcomes of patients who developed immune-related adverse events (irAEs) that required permanent treatment discontinuation. Methods: This national, multicenter study included 25 patients with metastatic NSCLC from four tertiary oncology centers in Turkey. All patients received nivolumab monotherapy and discontinued treatment because of irAEs. Long-term survival was analyzed using Kaplan-Meier methods and compared indirectly with historical benchmarks. Results: The median overall survival (OS) was 35.73 months (95% CI: 30.06-41.40). The 2-year and 5-year OS rates were 78.9% and 27.0%, respectively. Median progression-free survival (PFS) was 16.23 months. Pneumonitis was the most frequent irAE (48%). Liver metastases significantly reduced OS (23.93 vs. 38.50 months, p = 0.005). In univariate analysis, ECOG 2 status (HR:22.07), bone metastases (HR:3.52), and subsequent systemic therapy (HR:30.19) weresignificant predictors of progression. Conclusions: Patients with metastatic NSCLC who discontinue nivolumab due to irAEs achieve notable survival outcomes, suggesting that treatment-limiting toxicity may signal a robust and durable antitumor immune response. These findings, though limited by a small cohort, highlight a distinct responder phenotype in real-world clinical practice.