As reported in The Lancet Oncology by Özgüroğlu et al, extended follow-up of the phase III EMPOWER-Lung 1 trial has shown continued benefit in overall and progression-free survival with first-line cemiplimab-rwlc vs chemotherapy in patients with advanced non–small cell lung cancer (NSCLC) with PD-L1 expression of at least 50% and no EGFR, ALK, or ROS1 aberrations. The primary analysis of the trial supported the February 2021 approval of cemiplimab in this setting.
Study Details
In the open-label trial, 712 patients with PD-L1 expression of at least 50% (intent-to-treat [ITT] population) were randomly assigned between May 2017 and March 2020 to receive cemiplimab at 50 mg every 3 weeks for up to 108 weeks (n = 357) or investigator’s choice of platinum-doublet chemotherapy (n = 355). Because not all patient samples were consistently processed using assay instructions for use, the current analysis includes 284 patients in the cemiplimab group and 281 patients in the chemotherapy group who had PD-L1 expression of at least 50% on verified instruction-for-use testing.
The primary endpoints were overall survival and progression-free survival assessed by blinded independent central review. The current analysis provides outcomes at 35 months of follow-up and describes the effect of adding chemotherapy to cemiplimab at the time of disease progression.
Key Findings
At a median follow-up of 35 months among patients with verified PD-L1 expression of at least 50%, the median overall survival was 26.1 months (95% confidence interval [CI] = 22.1–31.8 months) in the cemiplimab group vs 13.3 months (95% CI = 10.5–16.2 months) in the chemotherapy group (hazard ratio [HR] = 0.57, 95% CI = 0.46–0.71, P < .0001). Median progression-free survival was 8.1 months (95% CI = 6.2–8.8 months) in the cemiplimab group vs 5.3 months (95% CI = 4.3–6.1 months) in the chemotherapy group (HR = 0.51, 95% CI = 0.42–0.62, P < .0001). Among 64 patients who continued cemiplimab beyond disease progression with the addition of histology-specific chemotherapy as second-line therapy, median progression-free survival was 6.6 months (95% CI = 6.1–9.3 months), and median overall survival was 27.4 months (95% CI = 23.0–31.8 months).
In the ITT population, median overall survival was 23.4 months (95% CI = 19.4–27.4 months) in the cemiplimab group vs 13.7 months (95% CI = 11.2–16.2 months) in the chemotherapy group (HR = 0·63, 95% CI = 0.52–0.77, P < .0001). Median progression-free survival was 6.3 months (95% CI = 4.6–8.3 months) in the cemiplimab group vs 5.3 months (95% CI = 4.3–6.0 months) in the chemotherapy group (HR = 0.56, 95% CI = 0.47–0.67, P < .0001).
No new safety signals were identified.
The investigators concluded: “At 35 months’ follow-up, the survival benefit of cemiplimab for patients with advanced non–small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non–small-cell lung cancer.”
Mustafa Özgüroğlu, MD, of Istanbul University Cerrahpaşa, Turkey, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Regeneron Pharmaceuticals and Sanofi. For full disclosures of the study authors, visit thelancet.com.
