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 < .0001), “single-site” irAEs (P < .0001), endocrine (P = .0043) and skin irAEs (P = .0005). Longer PFS was related to irAEs of any grade (P < .0001), “single-site” irAEs (P < .0001), “multiple-site” irAEs (P = .0374), endocrine irAEs (P = .0084) and skin irAEs (P = .0001). Longer OS was related to irAEs of any grade (P < .0001), “single-site” irAEs (P < .0001), endocrine irAEs (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. The aim of this study was to investigate with a large sample size, the predictive and prognostic positive roles of occurrence of immune-related adverse events in patients with non–small-cell lung cancer treated with PD-1 inhibitors. The study confirmed that immune-related adverse events are independent predictors of higher overall response rate, longer progression-free survival and longer overall survival.
Correlations Between the Immune-related Adverse Events Spectrum and Efficacy of Anti-PD1 Immunotherapy in NSCLC Patients / Cortellini, A.; Chiari, R.; Ricciuti, B.; Metro, G.; Perrone, F.; Tiseo, M.; Bersanelli, M.; Bordi, P.; Santini, D.; Giusti, R.; Grassadonia, A.; Di Marino, P.; Tinari, N.; De Tursi, M.; Zoratto, F.; Veltri, E.; Malorgio, F.; Garufi, C.; Russano, M.; Anesi, C.; Zeppola, T.; Filetti, M.; Marchetti, P.; Berardi, R.; Rinaldi, S.; Tudini, M.; Silva, R. R.; Pireddu, A.; Atzori, F.; Iacono, D.; Migliorino, M. R.; Porzio, G.; Cannita, K.; Ficorella, C.; Buti, S.. - In: CLINICAL LUNG CANCER. - ISSN 1525-7304. - 20:4(2019), pp. 237-247.e1. [10.1016/j.cllc.2019.02.006]