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.

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.