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.

Abstract

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.

• Authors: Alessio Cortellini, Alex Friedlaender, Giuseppe L Banna, Giampiero Porzio, Melissa Bersanelli, Federico Cappuzzo, Joachim G J V Aerts, Raffaele Giusti, Emilio Bria, Diego Cortinovis, Francesco Grossi, Maria R Migliorino, Domenico Galetta, Francesco Passiglia, Rossana Berardi, Francesca Mazzoni, Vincenzo Di Noia, Diego Signorelli, Alessandro Tuzi, Alain Gelibter, Paolo Marchetti, Marianna Macerelli, Francesca Rastelli, Rita Chiari, Danilo Rocco, Alessandro Inno, Pietro Di Marino, Giovanni Mansueto, Federica Zoratto, Matteo Santoni, Marianna Tudini, Michele Ghidini, Marco Filetti, Annamaria Catino, Pamela Pizzutilo, Luca Sala, Mario Alberto Occhipinti, Fabrizio Citarella, Marco Russano, Mariangela Torniai, Luca Cantini, Alessandro Follador, Vincenzo Sforza, Olga Nigro, Miriam G Ferrara, Ettore D'Argento, Alessandro Leonetti, Linda Pettoruti, Lorenzo Antonuzzo, Simona Scodes, Lorenza Landi, Giorgia Guaitoli, Cinzia Baldessari, Federica Bertolini, Luigi Della Gravara, Maria Giovanna Dal Bello, Robert A Belderbos, Marco De Filippis, Cristina Cecchi, Serena Ricciardi, Clelia Donisi, Alessandro De Toma, Claudia Proto, Alfredo Addeo, Ornella Cantale, Biagio Ricciuti, Carlo Genova, Alessandro Morabito, Daniele Santini, Corrado Ficorella, Katia Cannita
• Journal: Clinical lung cancer (Clin Lung Cancer) Vol. 21 Issue 6 Pg. 498-508.e2 (11 2020) ISSN: 1938-0690 [Electronic] United States
• PMID: 32680806 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Immunological
• B7-H1 Antigen
• CD274 protein, human
• pembrolizumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (adverse effects)
• Antineoplastic Agents, Immunological (adverse effects)
• B7-H1 Antigen (metabolism)
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism, pathology)
• Carcinoma, Squamous Cell (drug therapy, metabolism, pathology)
• Drug-Related Side Effects and Adverse Reactions (etiology, pathology)
• Female
• Follow-Up Studies
• Humans
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Male
• Middle Aged
• Prognosis
• Retrospective Studies
• Survival Rate