The FDA has approved cemiplimab-rwlc (Libtayo®, Regeneron Pharmaceuticals, Inc.), a programmed cell death protein 1 (PD-1) inhibitor, for the first-line treatment of patients with advanced non-small lung cancer cell (NSCLC) whose tumors express programmed death ligand 1 (PD-L1) in at least 50% of their cells and whose tumors do not have aberrations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or C-ROS oncogene 1 (ROS1).
"An estimated 25% to 35% of advanced NSCLC cases are expected to test positive for PD-L1 in at least 50% of tumor cells," note Ahmet Sezer, MD, Professor in the Department of Medical Oncology at Başkent University in Adana, Turkey, and colleagues in their recent publication in The Lancet of results of the phase 3 EMPOWER-Lung 1 trial (NCT03088540), on which the approval was based. "Cemiplimab monotherapy significantly improved overall survival and progression-free survival compared with chemotherapy in patients with advanced non–small-cell lung cancer with PD-L1 of at least 50%, providing a potential new treatment option for this patient population."
EMPOWER-Lung 1 enrolled 710 patients with histologically or cytologically confirmed stage IIIB, IIIC, or IV squamous or non-squamous NSCLC and high PD-L1 expression as assessed by immunohistochemistry of tumor samples using a 22C3 pharmDx assay (Dako Omnis, Agilent). Patients with stage IIIB or IIIC disease were not candidates for definitive chemoradiotherapy, and patients with stage IV disease were untreated but could be eligible if they had received adjuvant or neoadjuvant chemotherapy and met protocol criteria. Patients were randomly assigned in a 1:1 ratio to receive cemiplimab 350 mg every three weeks for up to 108 weeks or platinum-doublet chemotherapy for four to six cycles. The study's coprimary end points were overall survival and progression-free survival.
In the intention-to-treat population of 710 patients, followed for a median of 13.1 months, cemiplimab improved median overall survival compared with chemotherapy (22.1 vs 14.3 months). Median progression-free survival was 6.2 months for patients receiving cemiplimab versus 5.6 months for chemotherapy. Monitoring of samples during the trial revealed that some tumor samples from patients were not correctly analyzed according to assay instructions. As a result, a subpopulation in the study was prespecified to only include 563 patients with PD-L1 ≥50% using assay results correctly analyzed according to manufacturer's instructions and designated the PD-L1 ≥50% population. In the population with PD-L1 ≥50%, with a median follow-up of 10.8 months for cemiplimab and a median follow-up of 10.9 months for chemotherapy, cemiplamab was superior to chemotherapy for both median overall survival (not reached vs 14.2 months) and median progression-free survival (8.2 vs 5.7 months).
Grade 3/4 treatment-emergent adverse events occurred in 28% of patients treated with cemiplimab and in 39% of those treated with chemotherapy, with the most common grade 3/4 events in the cemiplimab group including pneumonia (5%), anemia (3%), and hyponatremia (3%). Grade 3/4 treatment-related adverse events occurred in 12% of patients treated with cemiplimab and 37% of patients treated with chemotherapy; those that affected at least 1% of patients treated with cemiplimab included increased aspartate aminotransferase and pneumonia.
"Treatment with cemiplimab resulted in significantly longer overall survival and progression-free survival, reducing the risk of death by 43.4% in the PD-L1 of at least 50% population and by 32.4% in the intention-to-treat population," conclude Dr. Sezer and colleagues. "The results of EMPOWER-Lung 1 showed a clinically meaningful and statistically significant improvement in overall survival and progression-free survival with first-line cemiplimab monotherapy over platinum-doublet chemotherapy in patients with advanced non-small-cell lung cancer with PD-L1 of at least 50%, despite a high crossover rate and broadened inclusion criteria."
The recommended dose of cemiplimab-rwlc for patients with NSCLC is 350 mg every three weeks, administered intravenously over 30 minutes.
For More Information
Sezer A, Kilickap S, Gümüş M, et al (2021). Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet, 397(10274):592-604. DOI:10.1016/S0140-6736(21)00228-2US Food & Drug Administration (2021). FDA approves cemiplimab-rwlc for non-small cell lung cancer with high PD-L1 expression. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-cemiplimab-rwlc-non-small-cell-lung-cancer-high-pd-l1-expression
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