Cemiplimab Monotherapy for First-Line Treatment of Patients with Advanced NSCLC With PD-L1 Expression of 50% or Higher: Five-Year Outcomes of EMPOWER-Lung 1

Abstract

Introduction: Earlier results from the phase 3 EMPOWER-Lung 1 trial indicated significant survival benefits and a generally acceptable safety profile of first-line cemiplimab monotherapy versus chemotherapy for patients with advanced NSCLC with programmed cell death-ligand 1 (PD-L1) expression in 50% or more tumor cells and no EGFR, ALK, or ROS1 aberrations. Here, we report the five-year outcomes. Methods: Patients were randomized 1:1 to cemiplimab 350 mg intravenously every three weeks for two years or the investigator's choice of chemotherapy. The primary endpoints were overall survival (OS) and progression-free survival. Results: A total of 712 patients were randomized to cemiplimab (n = 357) or chemotherapy (n = 355). The median duration of follow-up was 59.6 months (interquartile range:55.1-66.7 months) at the data cutoff (January 16, 2024). In patients with verified 50% or higher PD-L1 (n = 565), median OS was 26.1 months for cemiplimab versus 13.3 months for chemotherapy (hazard ratio = 0.59, 95% confidence interval [CI]: 0.48-0.72); the median progression-free survival was 8.1 months versus 5.3 months (hazard ratio = 0.50, 95% confidence interval: 0.41-0.61); and the objective response rate was 46.5% versus 20.6%. The five-year OS probability was 29.0% for cemiplimab and 15.0% for chemotherapy. Improved survival outcomes were observed with both squamous and nonsquamous histology, and increasing activity of cemiplimab was correlated with higher PD-L1 expression, with the highest PD-L1 expression having the best outcome. The safety profile remains consistent with previous results. Grade 3 or higher treatment-related adverse events occurred in 18.3% of patients for cemiplimab and 39.9% for chemotherapy. Conclusions: At five-year follow-up, first-line cemiplimab monotherapy continued to show durable clinical benefits versus chemotherapy in patients with advanced NSCLC with 50% or higher PD-L1. Patients with 90% or higher PD-L1 derived the largest clinical benefits. (c) 2025 The Authors. Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).