Cemiplimab Monotherapy for First-Line Treatment of Patients with Advanced NSCLC with PD-L1 Expression ≥50%: 5-Year Outcomes of EMPOWER-Lung 1.

Abstract

Introduction: Earlier results from the phase 3 EMPOWER-Lung 1 trial demonstrated significant survival benefits and a generally acceptable safety profile of first-line cemiplimab monotherapy versus chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) expression in ≥50% of tumor cells and no EGFR, ALK, or ROS1 aberrations. Here, we report the 5-year outcomes.

Methods: Patients were randomized 1:1 to cemiplimab 350 mg intravenous every 3 weeks for 2 years or investigator's choice of chemotherapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS).

Results: A total of 712 patients were randomized to cemiplimab (n = 357) or chemotherapy (n = 355). 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 PD-L1 ≥50% (n = 565), median OS was 26.1 months for cemiplimab vs. 13.3 months for chemotherapy (hazard ratio [HR] 0.59, 95% confidence interval [CI]: 0.48-0.72); median PFS was 8.1 months versus 5.3 months (HR 0.50, 95% CI: 0.41-0.61); the objective response rate was 46.5% versus 20.6%. The 5-year OS probability was 29.0% for cemiplimab and 15.0% for chemotherapy. Improved survival outcomes were observed with both squamous and non-squamous 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 treatment-related adverse events occurred in 18.3% of patients for cemiplimab and 39.9% for chemotherapy.

Conclusions: At 5-year follow-up, first-line cemiplimab monotherapy continued to show durable clinical benefits versus chemotherapy in patients with advanced NSCLC with PD-L1 ≥50%. Patients with PD-L1 ≥90% derived the largest clinical benefits.