Immune-Related Adverse Events Associated With Outcomes in Patients With NSCLC Treated With Anti-PD-1 Inhibitors: A Systematic Review and Meta-Analysis

Background and Objective Although anti-programmed cell death protein 1 (PD-1) antibodies have exerted remarkable anticancer activity in non-small cell lung cancer (NSCLC), it remains a challenge to identify patients who can benefit from these treatments. Immune-related adverse events (irAEs) may be associated with improved clinical outcomes after immune checkpoint inhibition. However, no conclusive evidence of this correlation has been summarized in patients with NSCLC receiving PD-1 inhibitors. We performed a systematic review and meta-analysis to evaluate the association between irAEs induced by anti-PD-1 antibodies and clinical outcomes in patients with NSCLC. Methods Various databases were searched from their inception to January 9, 2021, followed by screening of eligible studies. Hazard ratios were used for the pooled analysis of overall survival (OS) and progression-free survival (PFS), while odds ratios (ORs) were utilized to pool objective response rates (ORRs) and disease control rates (DCRs). A random-effects model was applied to all analyses. Results A total of 26 cohorts, including 8,452 patients with NSCLC receiving anti-PD-1 antibodies, were enrolled in the study. Significantly improved OS (HR: 0.51; 95% CI: 0.44-0.60; P 0.01) and PFS (HR: 0.50; 95% CI: 0.43-0.58; P 0.01) were found to be correlated with irAEs. In addition, patients with NSCLC who developed irAEs after PD-1 inhibition demonstrated better responses to therapies, confirmed by pooled ORs of ORRs (OR: 3.41; 95% CI: 2.66-4.35; P 0.01) and DCRs (OR: 4.08; 95% CI: 2.30-7.24; P 0.01). Furthermore, subgroup analysis suggested that both skin and endocrine irAEs are closely correlated with a reduced risk of death, whereas pulmonary irAEs showed no association with longer OS. Conclusions In patients with NSCLC treated with anti-PD-1 therapies, the presence of irAEs was strongly correlated with better survival and response, suggesting its potential role as a predictive biomarker for outcomes after PD-1 inhibition.