EMPOWER-Lung 1: First-Line Cemiplimab Shows ‘Durable Clinical Benefits’ in NSCLC

First-line cemiplimab monotherapy “continued to show durable clinical benefits” in patients who have advanced non–small cell lung cancer (NSCLC) with PD-L1 expression of at least 50%, according to 5-year follow-up from the phase 3 EMPOWER-Lung 1 trial.

Saadettin Kilickap, MD, of the Istinye University Faculty of Medicine, and colleagues published the 5-year outcomes from the trial in the Journal of Thoracic Oncology. They explained that earlier results from the phase 3 trial showed “significant survival benefits and a generally acceptable safety profile of first-line cemiplimab monotherapy versus chemotherapy” in patients with advanced NSCLC with PD-L1 expression in at least 50% of tumor cells and no EGFR, ALK, or ROS1 aberrations.

The study investigators randomized 712 patients 1:1 to receive IV cemiplimab 350 mg (n=357) every 3 weeks for 2 years or investigator’s choice of chemotherapy (n=355). The primary end points of the EMPOWER-Lung 1 trial were overall survival (OS) and progression-free survival (PFS). The median duration of follow-up was 59.6 months at the data cutoff date of January 16, 2024.

Among the 565 patients with verified PD-L1 expression in at least 50% of tumor cells, the median OS was 26.1 months in those who were receiving cemiplimab, nearly double the median OS of 13.3 months in those receiving chemotherapy (hazard ratio [HR], 0.59; 95% CI, 0.48-0.72). The 5-year OS probability was 29% among patients receiving cemiplimab, compared with 15% among those receiving 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,” Dr. Kilickap and colleagues explained.

The median PFS was numerically higher in patients receiving cemiplimab (8.1 months) than in those receiving chemotherapy (5.3 months; HR, 0.50; 95% CI, 0.41-0.61). The objective response rate was 46.5% among patients receiving cemiplimab, compared with 20.6% among those receiving chemotherapy.

The safety profile of cemiplimab “remains consistent with previous results,” with grade 3 or higher treatment-related adverse events reported in 18.3% of patients receiving cemiplimab and 39.9% of those receiving chemotherapy.

Based on these findings from the 5-year follow-up, the study investigators concluded that first-line monotherapy with cemiplimab monotherapy “continued to show durable clinical benefits versus chemotherapy” in patients who have advanced NSCLC with PD-L1 expression of at least 50% and that patients with PD-L1 expression of at least 90% “derived the largest clinical benefits” from cemiplimab.

Reference

Kilickap S, Baramidze A, Sezer A, et al. Cemiplimab monotherapy for first-line treatment of patients with advanced NSCLC with PD-L1 expression ≥50%: 5-year outcomes of EMPOWER-Lung 1. Journal of Thoracic Oncology. Published online March 19, 2025. doi:https://doi.org/10.1016/j.jtho.2025.03.033