Cemiplimab Shows 5-Year Survival Benefit in Advanced NSCLC With High PD-L1 Expression

Cemiplimab monotherapy provided durable survival benefits compared with chemotherapy for people with advanced non–small cell lung cancer (NSCLC) whose tumors expressed programmed cell death-ligand 1 (PD-L1) in at least 50% of cells, according to the 5-year analysis of the phase 3 EMPOWER-Lung 1 trial (NCT03409614).1

In this analysis, cemiplimab was generally better tolerated than chemotherapy, with grade 3 or higher treatment-related adverse events occurred in 18.3% vs 39.9%. | Image credit: PRASANNAPIX - stock.adobe.com

Immune checkpoint inhibitors targeting PD-1 and PD-L1 have become a standard of care for advanced NSCLC without driver mutations. Cemiplimab, a fully human PD-1 inhibitor, was previously shown to improve outcomes compared with chemotherapy, and long-term data were needed to determine whether those benefits persisted over time.1,2

Cemiplimab (Librayo; Regeneron) is approved for several advanced or metastatic cancers, including cutaneous squamous cell carcinoma, basal cell carcinoma, NSCLC, and cervical cancer. Cemiplimab is administered as a 30-minute intravenous infusion in a hospital or clinic.2

The EMPOWER-Lung 1 study was designed to address this question by comparing cemiplimab with histology-appropriate platinum-based chemotherapy in the first-line setting.1

The study enrolled 712 adults with untreated locally advanced or metastatic NSCLC across 138 sites in 24 countries. All participants had PD-L1 expression of 50% or greater and lacked EGFR, ALK, or ROS1 aberrations. Patients were randomized 1:1 to receive cemiplimab 350 mg intravenously every 3 weeks for up to 2 years or standard chemotherapy, with crossover to cemiplimab permitted for those initially assigned to chemotherapy. The primary end points were overall survival (OS) and progression-free survival (PFS), and secondary end points included objective response rate (ORR) and duration of response (DOR).

After a median follow-up of nearly 5 years, cemiplimab demonstrated clinically meaningful and sustained improvements in OS, PFS, and response durability. Among patients with verified PD-L1 expression of 50% or greater, the median OS was 26.1 months with cemiplimab compared with 13.3 months for chemotherapy, translating to an HR of 0.59. The 5-year OS probability was 29% for cemiplimab vs 15% for chemotherap, and the median PFS was 8.1 months with cemiplimab vs 5.3 months with chemotherapy. The ORR was more than double with cemiplimab at 46.5% compared with 20.6% with chemotherapy, and responses lasted substantially longer with a median DOR of 24.1 months vs 5.9 months.

The survival benefit of cemiplimab extended across disease subtypes. In squamous NSCLC, the median OS was 22.7 months with cemiplimab and 13.5 months with chemotherapy, while in nonsquamous disease, the median OS was 28.7 months compared with 13.0 months, respectively. Exploratory analyses also showed that higher PD-L1 expression correlated with greater benefit. Patients with PD-L1 expression of at least 90% had a median OS of 38.8 months and a 5-year survival probability approaching 40%, outcomes not previously reported in advanced NSCLC without actionable genomic alterations.

Cemiplimab was generally better tolerated than chemotherapy. Grade 3 or higher treatment-related adverse events occurred in 18.3% of patients who received cemiplimab compared with 39.9% of those treated with chemotherapy. Common toxicities with chemotherapy included anemia, neutropenia, and thrombocytopenia, whereas cemiplimab was associated with a smaller number of severe immune-related events, including rare cases of nephritis and myocarditis. No new safety signals were identified during long-term follow-up.

The trial had some limitations, including the exploratory nature of analyses by PD-L1 subgroups and a relatively low proportion of female participants, likely reflecting smoking prevalence and NSCLC epidemiology in participating regions. Despite these factors, the 5-year results support cemiplimab as a first-line option for advanced NSCLC with high PD-L1 expression, particularly in individuals with the highest PD-L1 levels, where the greatest survival gains were observed.

Reference
1. Kilickap S, Baramidze A, Sezer A, et al. 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. J Thorac Oncol. 2025;20(7):941-954. doi:10.1016/j.jtho.2025.03.033

2. Regeneron. Libtayo is indicated in the following tumor types. Libtayo website. Accessed September 8, 2025. https://www.libtayohcp.com/product-support