Correlations Between the Immune-related Adverse Events Spectrum and Efficacy of Anti-PD1 Immunotherapy in NSCLC Patients

Abstract Background Immune-related adverse events (irAEs) developed during immunotherapy with anti-PD-1 agents, could be a predictive surrogate marker of clinical benefit in patients with advanced non–small-cell lung cancer (NSCLC). Methods Patients with NSCLC, treated with anti-PD-1 agents, were retrospectively evaluated. Univariate and multivariate analyses were performed to evaluate the relationships between types of irAEs (differentiated according to system/organ involved and to single-site/multiple-site), overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). We further performed a 6-week landmark analysis. Results A total of 559 patients were enrolled; 231 patients (41.3%) developed irAEs of any grade and 50 patients (8.9%) G3/G4 events; 191 of them (82.6%) developed “single-site” irAEs and 40 (17.4%) “multiple-site” irAEs. At multivariate analysis, higher ORR was related to irAEs of any grade ( P P P = .0043) and skin irAEs ( P = .0005). Longer PFS was related to irAEs of any grade ( P P P = .0374), endocrine irAEs ( P = .0084) and skin irAEs ( P = .0001). Longer OS was related to irAEs of any grade ( P P P = .0044), gastrointestinal irAEs ( P = .0437), skin irAEs ( P = .0006), and others irAEs ( P = .0378). At the 6-week landmark analysis, irAEs of any grade was confirmed an independent predictor of higher ORR, longer PFS, and longer OS. Conclusion Our study confirmed that irAEs are concordantly related to higher ORR, longer PFS, and longer OS with anti-PD-1 immunotherapy in patients with NSCLC.