Immune-related Adverse Events of Pembrolizumab in a Large Real-world Cohort of Patients With NSCLC With a PD-L1 Expression ≥ 50% and Their Relationship With Clinical Outcomes.

Cortellini, Alessio; Friedlaender, Alex; Banna, Giuseppe L; Porzio, Giampiero; Bersanelli, Melissa; Cappuzzo, Federico; Aerts, Joachim G J V; Giusti, Raffaele; Bria, Emilio; Cortinovis, Diego; Grossi, Francesco; Migliorino, Maria R; Galetta, Domenico; Passiglia, Francesco; Berardi, Rossana; Mazzoni, Francesca; Di Noia, Vincenzo; Signorelli, Diego; Tuzi, Alessandro; Gelibter, Alain; Marchetti, Paolo; Macerelli, Marianna; Rastelli, Francesca; Chiari, Rita; Rocco, Danilo; Inno, Alessandro; Di Marino, Pietro; Mansueto, Giovanni; Zoratto, Federica; Santoni, Matteo; Tudini, Marianna; Ghidini, Michele; Filetti, Marco; Catino, Annamaria; Pizzutilo, Pamela; Sala, Luca; Occhipinti, Mario Alberto; Citarella, Fabrizio; Marco, Russano; Torniai, Mariangela; Cantini, Luca; Follador, Alessandro; Sforza, Vincenzo; Nigro, Olga; Ferrara, Miriam G; D'Argento, Ettore; Leonetti, Alessandro; Pettoruti, Linda; Antonuzzo, Lorenzo; Scodes, Simona; Landi, Lorenza; Guaitoli, Giorgia; Baldessari, Cinzia; Bertolini, Federica; Della Gravara, Luigi; Dal Bello, Maria Giovanna; Belderbos, Robert A; De Filippis, Marco; Cecchi, Cristina; Ricciardi, Serena; Donisi, Clelia; De Toma, Alessandro; Proto, Claudia; Addeo, Alfredo; Cantale, Ornella; Ricciuti, Biagio; Genova, Carlo; Morabito, Alessandro; Santini, Daniele; Ficorella, Corrado; Cannita, Katia

BACKGROUND The role of immune-related adverse events (irAEs), as a surrogate predictor of the efficacy of checkpoint inhibitors, has not yet been described in the setting of first-line, single-agent pembrolizumab for patients with metastatic non-small-cell lung-cancer (NSCLC) with a programmed death-ligand 1 (PD-L1) expression of ≥ 50%. PATIENTS AND METHODS We previously conducted a multicenter retrospective analysis in patients with treatment-naive metastatic NSCLC and a PD-L1 expression of ≥ 50% receiving first-line pembrolizumab. Here, we report the results of the irAE analysis and the potential correlation between irAEs and clinical outcomes. RESULTS A total of 1010 patients were included in this analysis; after a 6-week landmark selection, 877 (86.8%) patients were included in the efficacy analysis. Any grade irAEs (P < .0001), grade 3/4 irAEs (P = .0025), leading to discontinuation irAEs (P = .0144), multiple-site and single-site irAEs (P < .0001), cutaneous irAEs (P = .0001), endocrine irAEs (P = .0227), pulmonary irAEs (P = .0479), and rheumatologic irAEs (P = .0018) were significantly related to a higher objective response rate. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0005), cutaneous irAEs (P = .0042), endocrine irAEs (P < .0001), gastrointestinal irAEs (P = .0391), and rheumatologic irAEs (P = .0086) were significantly related to progression-free survival. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0003), cutaneous irAEs (P = .0002), endocrine irAEs (P = .0001), and rheumatologic irAEs (P = .0214) were significantly related to overall survival. CONCLUSIONS This study confirms the feasibility and the safety of first-line, single-agent pembrolizumab, in a large, real-world cohort of patients with NSCLC with PD-L1 expression ≥ 50%. The occurrence of irAEs may be a surrogate of clinical activity and improved outcomes in this setting.