Abstract
BACKGROUND: Recent studies have demonstrated that high-dose corticosteroids and second-line immunosuppressants may impair survival of patients with immune-related adverse events (irAEs) upon treatment with immune checkpoint inhibitors (ICIs). In non-small-cell lung cancer (NSCLC), this has not been studied in sufficiently powered studies. This study assessed the association of corticosteroid dose and second-line immunosuppressants for irAEs with survival outcomes in patients with stage IV NSCLC treated with ICIs. PATIENTS AND METHODS: Patients with stage IV NSCLC treated with ICI-based regimens between 2015 and 2022 in the first or second line who received systemic immunosuppressants for irAEs were retrospectively included from 17 hospitals in eight countries worldwide. Associations of corticosteroid peak and cumulative dose, and use of second-line immunosuppressants with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were assessed using Cox proportional hazards regression. RESULTS: Of 419 included patients, 339 (80.9%) were treated with corticosteroids only and 80 (19.1%) received second-line immunosuppressants. Higher corticosteroid peak dose was associated with impaired OS [adjusted hazard ratio (HR(adj)) 1.63, 95% confidence interval (CI) 1.27-2.08 for an increase by 80 mg prednisolone equivalent] and CSS (HR(adj) 1.54, 95% CI 1.13-2.08), but not PFS (HR(adj) 1.05, 95% CI 0.75-1.48). The cumulative corticosteroid dose and use of second-line immunosuppressants were not associated with survival. CONCLUSION: Treatment with high corticosteroid peak dose for irAEs is associated with impaired survival in patients with stage IV NSCLC receiving ICI. Treatment of severe irAEs often requires high doses of corticosteroids. However, clinicians should weigh the unfavorable effects of high peak doses against the need for rapid irAE management.