Biagio Ricciuti1,2, Carlo Genova3, Andrea De Giglio4, Maria Bassanelli5, Maria Giovanna Dal Bello3, Giulio Metro4, Marta Brambilla4, Sara Baglivo4, Francesco Grossi3, Rita Chiari4. 1. Medical Oncology, Santa Maria della Misericordia Hospital, Piazzale Menghini, 06129, Perugia, Italy. biagio.ricciuti@gmail.com. 2. Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, via Dottori, 1, 06156, Perugia, Italy. biagio.ricciuti@gmail.com. 3. Lung Cancer Unit, Ospedale Policlinico San Martino, Largo R. Renzi 10, 16132, Genoa, Italy. 4. Medical Oncology, Santa Maria della Misericordia Hospital, Piazzale Menghini, 06129, Perugia, Italy. 5. Medical Oncology, San Camillo de Lellis Hospital, via del Terminillo 42, 02100, Rieti, Italy.
Abstract
PURPOSE: Immune-checkpoint inhibitors (ICIs) represent the standard of care for platinum-pretreated advanced non-small cell lung cancer patients. Patients treated with ICIs may experience immune-related adverse events (irAEs), that might reflect antitumor responses. Here we evaluated nivolumab efficacy according to the development of irAEs. METHODS: We conducted a multicenter retrospective study of patients with advanced NSCLC treated with nivolumab between October 2013 and September 2017. IrAEs were defined as AEs having immunological basis that required intensive monitoring and interventions. RESULTS: Among 195 patients [median (range) age, 63 (30-84) years; 128 men (65.6%), 67 women (34.4%)], irAEs were observed in 85 patients (43.6%), including 15 patients (7.6%) with grade 3 or 4 events. Median PFS was 5.7 months in irAEs group compared to 2.0 months of no-irAEs group [HR: 0.41 (95% CI 0.3-0.57), P < 0.0001]. Median OS was 17.8 months compared to 4.0 months of no-irAEs group [HR: 0.33 (95% CI 0.23-0.47), P < 0.0001]. IrAEs were significantly associated with improved clinical outcome in 12- and 6-week landmark analysis. Patients who developed ≥ 2 irAEs during treatment (n: 37) had a significantly longer median PFS and OS compared to those with one (n: 48) or none AEs (n: 110) (PFS: 8.5 months vs. 4.6 vs. 2.0, P < 0.0001; OS: 26.8 months vs. 11.9 vs. 4.0, P < 0.0001). Multivariable analysis revealed that irAEs were positively associated with PFS [HR: 0.48 (95% CI 0.34-0.67), P < 0.0001] and OS [HR: 0.38 (95% CI 0.26-0.56), P < 0.0001]. CONCLUSION: In this study we confirmed that the development of irAEs was a strong predictor of survival outcomes in NSCLC patients treated with nivolumab monotherapy in landmark and multivariable models. Patients who experienced ≥ 2 irAEs had a more pronounced survival benefit compared to those with 1 irAE further suggesting a mechanistic association between irAEs and immunotherapy efficacy.
PURPOSE: Immune-checkpoint inhibitors (ICIs) represent the standard of care for platinum-pretreated advanced non-small cell lung cancerpatients. Patients treated with ICIs may experience immune-related adverse events (irAEs), that might reflect antitumor responses. Here we evaluated nivolumab efficacy according to the development of irAEs. METHODS: We conducted a multicenter retrospective study of patients with advanced NSCLC treated with nivolumab between October 2013 and September 2017. IrAEs were defined as AEs having immunological basis that required intensive monitoring and interventions. RESULTS: Among 195 patients [median (range) age, 63 (30-84) years; 128 men (65.6%), 67 women (34.4%)], irAEs were observed in 85 patients (43.6%), including 15 patients (7.6%) with grade 3 or 4 events. Median PFS was 5.7 months in irAEs group compared to 2.0 months of no-irAEs group [HR: 0.41 (95% CI 0.3-0.57), P < 0.0001]. Median OS was 17.8 months compared to 4.0 months of no-irAEs group [HR: 0.33 (95% CI 0.23-0.47), P < 0.0001]. IrAEs were significantly associated with improved clinical outcome in 12- and 6-week landmark analysis. Patients who developed ≥ 2 irAEs during treatment (n: 37) had a significantly longer median PFS and OS compared to those with one (n: 48) or none AEs (n: 110) (PFS: 8.5 months vs. 4.6 vs. 2.0, P < 0.0001; OS: 26.8 months vs. 11.9 vs. 4.0, P < 0.0001). Multivariable analysis revealed that irAEs were positively associated with PFS [HR: 0.48 (95% CI 0.34-0.67), P < 0.0001] and OS [HR: 0.38 (95% CI 0.26-0.56), P < 0.0001]. CONCLUSION: In this study we confirmed that the development of irAEs was a strong predictor of survival outcomes in NSCLCpatients treated with nivolumab monotherapy in landmark and multivariable models. Patients who experienced ≥ 2 irAEs had a more pronounced survival benefit compared to those with 1 irAE further suggesting a mechanistic association between irAEs and immunotherapy efficacy.
Entities:
Keywords:
Immune-related AEs; Nivolumab; Non-small cell lung cancer
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