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

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.