Association between immune-related adverse events and prognosis in patients with advanced non-small cell lung cancer: a systematic review and meta-analysis

Background: The emergence of immune checkpoint inhibitors (ICIs) provides a variety of options for patients with advanced non-small-cell lung cancer (NSCLC). After the application of ICIs, the immune system of patients was highly activated, and immune-related adverse events (irAEs) could occur in some organ systems, and irAEs seemed to be associated with the survival prognosis of patients. Therefore, we evaluated the association between survival outcomes and irAEs in NSCLC patients and conducted a systematic review and meta-analysis. Methods: We conducted systematic reviews of PubMed, Embase, Cochrane, and Web of Science databases until December 2021. The forest map was constructed by combining the hazard ratio (HR) and 95% confidence interval (CI). I-2 estimated the heterogeneity between studies. A meta-analysis was performed using R 4.2.1 software. Results: Eighteen studies included 4808 patients with advanced NSCLC. In pooled analysis, the occurrence of irAEs was found to be a favorable factor for improved prognosis (PFS: HR: 0.48, 95% CI: 0.41-0.55, P <0.01; OS: HR: 0.46, 95% CI: 0.42-0.52, P <0.01). In subgroup analyses, cutaneous irAE, gastrointestinal irAE, endocrine irAE and grade >= 3 irAEs were associated with improvements in PFS and OS, but pulmonary and hepatic irAEs were not. Conclusion: Existing evidence suggests that the occurrence of irAEs may be a prognostic biomarker for advanced NSCLC. However, further research is needed to explore the prospect of irAEs as a prognostic biomarker in patients undergoing immunotherapy. Systematic review registration: https://www.crd.york.ac.uk/PROSPEROFILES/405333_STRATEGY_20240502.pdf, identifier CRD42023405333.