Effect of Immune-Related Adverse Events and Pneumonitis on Prognosis in Advanced Non–Small Cell Lung Cancer: A Comprehensive Systematic Review and Meta-analysis

Objective: The correlation between immune-related adverse events (irAEs) and prognosis remains controversial in advanced non–small cell lung cancer (NSCLC). The aim of this study was to systematically evaluate the effect of irAEs, especially checkpoint inhibitor pneumonitis (CIP), on the survival and treatment response in advanced NSCLC. Methods: The primary outcomes were overall survival (OS) and objective response rate (ORR). Databases were searched for relevant studies, and meta-analysis was conducted with RevMan. Results: A total of 51 studies involving 12,600 participants were included. The development of irAEs had an advantageous effect on OS and ORR in advanced NSCLC (OS: hazard ratio [HR], 0.56 [95% confidence interval [CI] 0.46 to 0.67]; ORR: odds ratio [OR], 3.13 [2.41 to 4.06]). The occurrence of endocrine and skin irAEs had advantageous effects on both OS and ORR (endocrine OS, HR, 0.47 [–0.37 to 0.59]; endocrine ORR: OR, 1.90 [1.27 to 2.84]; skin OS: HR, 0.48 [0.38 to 0.61]; skin ORR: OR, 4.30 [2.68 to 6.91]). Severe-grade irAEs resulted in shorter OS than low-grade irAEs (HR, 1.49 [1.06, 2.09]), and multiple irAEs resulted in better ORR compared with 1 irAE (OR, 2.04 [1.41 to 2.94]). The occurrence of CIP had no significant effect on OS (HR, 1.14 [0.70 to 1.86]), but it was associated with better ORR (OR, 2.12 [1.06 to 4.25]). Severe-grade CIP had no effect on OS or ORR, but CIP leading to treatment discontinuation resulted in shorter OS (HR, 2.35 [1.17 to 4.72]). Conclusion: The development of irAEs had advantageous effects on survival and response in advanced NSCLC. CIP had no effect on survival, but it predicted better response.