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, A.; Friedlaender, A.; Banna, G. L.; Porzio, G.; Bersanelli, M.; Cappuzzo, F.; Aerts, J. G. J. V.; Giusti, R.; Bria, E.; Cortinovis, D.; Grossi, F.; Migliorino, M. R.; Galetta, D.; Passiglia, F.; Berardi, R.; Mazzoni, F.; Di Noia, V.; Signorelli, D.; Tuzi, A.; Gelibter, A.; Marchetti, P.; Macerelli, M.; Rastelli, F.; Chiari, R.; Rocco, D.; Inno, A.; Di Marino, P.; Mansueto, G.; Zoratto, F.; Santoni, M.; Tudini, M.; Ghidini, M.; Filetti, M.; Catino, A.; Pizzutilo, P.; Sala, L.; Occhipinti, M.; Citarella, F.; Marco, R.; Torniai, M.; Cantini, L.; Follador, A.; Sforza, V.; Nigro, O.; Ferrara, M. G.; D'Argento, E.; Leonetti, A.; Pettoruti, L.; Antonuzzo, L.; Scodes, S.; Landi, L.; Guaitoli, G.; Baldessari, C.; Bertolini, F.; Della Gravara, L.; Dal Bello, M. G.; Belderbos, R. A.; De Filippis, M.; Cecchi, C.; Ricciardi, S.; Donisi, C.; De Toma, A.; Proto, C.; Addeo, A.; Cantale, O.; Ricciuti, B.; Genova, C.; Morabito, A.; Santini, D.; Ficorella, C.; Cannita, K.

doi:10.1016/j.cllc.2020.06.010

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.

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, A.; Friedlaender, A.; Banna, G. L.; Porzio, G.; Bersanelli, M.; Cappuzzo, F.; Aerts, J. G. J. V.; Giusti, R.; Bria, E.; Cortinovis, D.; Grossi, F.; Migliorino, M. R.; Galetta, D.; Passiglia, F.; Berardi, R.; Mazzoni, F.; Di Noia, V.; Signorelli, D.; Tuzi, A.; Gelibter, A.; Marchetti, P.; Macerelli, M.; Rastelli, F.; Chiari, R.; Rocco, D.; Inno, A.; Di Marino, P.; Mansueto, G.; Zoratto, F.; Santoni, M.; Tudini, M.; Ghidini, M.; Filetti, M.; Catino, A.; Pizzutilo, P.; Sala, L.; Occhipinti, M.; Citarella, F.; Marco, R.; Torniai, M.; Cantini, L.; Follador, A.; Sforza, V.; Nigro, O.; Ferrara, M. G.; D'Argento, E.; Leonetti, A.; Pettoruti, L.; Antonuzzo, L.; Scodes, S.; Landi, L.; Guaitoli, G.; Baldessari, C.; Bertolini, F.; Della Gravara, L.; Dal Bello, M. G.; Belderbos, R. A.; De Filippis, M.; Cecchi, C.; Ricciardi, S.; Donisi, C.; De Toma, A.; Proto, C.; Addeo, A.; Cantale, O.; Ricciuti, B.; Genova, C.; Morabito, A.; Santini, D.; Ficorella, C.; Cannita, K.. - In: CLINICAL LUNG CANCER. - ISSN 1525-7304. - 21:6(2020), pp. 498-508.e2. [10.1016/j.cllc.2020.06.010]