New Paper Alert: EMPOWER-Lung 1 Trial: Cemiplimab Shows 5-Year Survival Benefit in Advanced NSCLC with High PD-L1 Expression

The EMPOWER-Lung 1 trial is a landmark phase 3 study evaluating cemiplimab, a PD-1 inhibitor, as a first-line monotherapy for patients with advanced non-small cell lung cancer (NSCLC) exhibiting high PD-L1 expression (≥50%). Conducted over a five-year period, the trial compared cemiplimab to standard chemotherapy, assessing overall survival (OS), progression-free survival (PFS), and safety outcomes. With a median OS of 26.1 months in the cemiplimab group versus 13.3 months in the chemotherapy group, the results highlight a significant survival advantage. This study underscores the importance of immunotherapy in NSCLC management and reinforces PD-L1 as a crucial biomarker for treatment selection.

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

Authors

Saadettin Kilickap, Ana Baramidze, Ahmet Sezer, Mustafa Özgüroğlu, Mahmut Gumus,  Igor Bondarenko, Miranda Gogishvili, Marina Nechaeva, Michael Schenker, Irfan Cicin,Ho Gwo Fuang, Yaroslav Kulyaba, Kasimova Zyuhal, Roxana-Ioana Scheusan , Marina Chiara Garassino, Yuntong Li, Cong Zhu, Manika Kaul, Javier Perez, Frank Seebach, Israel Lowy, Jean-Francois Pouliot, Eric Kim, Heather Magnan

Published in JTO, March 2025

Background

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. The expression of programmed cell death-ligand 1 (PD-L1) on tumor cells has been identified as a predictive biomarker for response to immunotherapies. Cemiplimab, a PD-1 inhibitor, has shown promise in enhancing survival outcomes for patients with advanced NSCLC exhibiting PD-L1 expression on ≥50% of tumor cells.

Methods of EMPOWER-lung 1  trial 

EMPOWER-Lung 1 trial is a phase 3 trial, which enrolled 712 patients with advanced NSCLC and PD-L1 expression ≥50%, without EGFR, ALK, or ROS1 aberrations. Participants were randomized in a 1:1 ratio to receive either cemiplimab (350 mg intravenously every 3 weeks for up to 2 years) or the investigator’s choice of chemotherapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS).​

Study Design of EMPOWER-lung 1 trial 

Patients were stratified based on histology (squamous vs. non-squamous) and geographic region. The trial employed a randomized, open-label design to objectively assess the efficacy and safety of cemiplimab compared to standard chemotherapy regimens.​

Results 

With a median follow-up duration of 59.6 months (interquartile range: 55.1–66.7 months) as of January 16, 2024, the study reported the following outcomes for patients with confirmed PD-L1 ≥50% (n = 565):​

• Overall Survival (OS): Median OS was 26.1 months for the cemiplimab group versus 13.3 months for the chemotherapy group (hazard ratio [HR] 0.59; 95% confidence interval [CI]: 0.48–0.72).​
  
• Progression-Free Survival (PFS): Median PFS was 8.1 months with cemiplimab compared to 5.3 months with chemotherapy (HR 0.50; 95% CI: 0.41–0.61).
• Objective Response Rate (ORR): 46.5% in the cemiplimab group versus 20.6% in the chemotherapy group.
• 5-Year OS Probability: 29.0% for patients treated with cemiplimab, compared to 15.0% for those receiving chemotherapy.

The survival benefits of cemiplimab were observed across both squamous and non-squamous histologies. Notably, patients with PD-L1 expression ≥90% experienced the most pronounced clinical benefits.​

Key Findings

The 5-year outcomes from the EMPOWER-Lung 1 trial affirm cemiplimab monotherapy as a durable and effective first-line treatment for patients with advanced NSCLC and high PD-L1 expression. These findings advocate for the integration of cemiplimab into standard treatment protocols for this patient population

• Efficacy Across Subgroups: Cemiplimab demonstrated consistent efficacy across different histological subtypes of NSCLC.​
• PD-L1 Expression Correlation: Higher PD-L1 expression levels correlated with improved responses to cemiplimab therapy.​
• Safety Profile: Grade ≥3 treatment-related adverse events occurred in 18.3% of patients receiving cemiplimab, compared to 39.9% in the chemotherapy group, indicating a more favorable safety profile for cemiplimab.

Key Takeaway Messages

• Cemiplimab offers a significant survival advantage over traditional chemotherapy for first-line treatment in advanced NSCLC patients with PD-L1 expression ≥50%
• The therapy is particularly effective in patients with PD-L1 expression levels ≥90%, underscoring the importance of biomarker testing in treatment planning.​

Cemiplimab’s favorable safety profile suggests it is a well-tolerated treatment option, with fewer high-grade adverse events compared to chemotherapy.​

You can read the full article here

Written by Sona Karamyan,MD