The FDA has granted approval of cemiplimab-rwlc (Libtayo®, Regeneron Pharmaceuticals, Inc.) in combination with platinum-based chemotherapy for treatment of advanced non–small cell lung cancer (aNSCLC) with no epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or ROS proto-oncogene 1 (ROS1) aberrations, and no prior systemic treatment. Cemiplimab-rwlc is a fully human immune checkpoint inhibitor targeting the programmed cell death receptor-1 (PD-1).
"Pembrolizumab and atezolizumab are both approved as first-line therapies in combination with platinum-based chemotherapy and other therapies for certain patient populations with metastatic NSCLC, although atezolizumab approval with platinum-doublet chemotherapy is limited to non-squamous histology," wrote Miranda Gogishvili, MD, a Medical Oncologist at the High Technology Medical Center, University Clinic in Tbilisi, Georgia, and colleagues, in their results of the EMPOWER-Lung 3 trial (NCT03409614), on which the approval was based. "Combinations of checkpoint inhibitors…are also approved for patients with advanced NSCLC irrespective of histology, but the clinical utility of these agents compared to single-agent checkpoint treatments alone or in combination with chemotherapy is unclear."
Safety and efficacy were measured in the phase 3, multicenter, double-blind trial, in which 446 patients were randomized 2:1 to receive either 350 mg of cemiplimab-rwlc or placebo, both in combination with platinum-based chemotherapy every three weeks for four cycles, followed by cemiplimab-rwlc or placebo in combination with maintenance chemotherapy. The primary end point measured was overall survival, with key secondary end points of progression-free survival and overall response rate assessed by blinded independent central review (BICR).
At a median follow up of 16.3 months in the cemiplimab-rwlc group and 16.7 months in the placebo group, overall survival saw a statistically significant improvement in those being treated with cemiplimab-rwlc (21.9 months) compared with those receiving placebo (13.0 months). Progression-free survival, as assessed by BICR, saw significant results as well, with those in the cemiplimab-rwlc arm having a median of 8.2 months compared with 5.0 months in the placebo arm. Finally, overall response rate, as assessed by BICR, was 43.3% in the cemiplimab-rwlc arm compared with 22.7% the placebo arm. The independent data monitoring committee (IDMC) ended the trial early due to meeting the preset efficacy criteria for overall survival.
The most common adverse events experienced in ≥15% of patients were alopecia, musculoskeletal pain, nausea, fatigue, peripheral neuropathy, and decreased appetite.
"This study fills a gap in the available evidence that is important for clinical practice and establishes a potential new standard-of-care treatment option for these patients," concluded Dr. Gogishvili and colleagues. "The results of EMPOWER-Lung 3 demonstrate that cemiplimab in combination with platinum-doublet chemotherapy is a potential first-line treatment option for patients with advanced squamous and non-squamous NSCLC, regardless of programmed cell death ligand-1 (PD-L1) expression level and without EGFR, ALK or ROS1 aberrations."
The recommended dosage of cemiplimab-rwlc is 350 mg via intravenous infusion every three weeks. When appropriate, information regarding dosing of cemiplimab-rwlc in combination with other agents can be found in the prescribing information.
For More Information
Gogishvili M, Melkadze T, Makharadze T, et al (2022). Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial. Nat Med. [Epub ahead of print] DOI:10.1038/s41591-022-01977-y
US Food and Drug Administration (2022). FDA approves cemiplimab-rwlc in combination with platinum-based chemotherapy for non-small cell lung cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cemiplimab-rwlc-combination-platinum-based-chemotherapy-non-small-cell-lung-cancer
Image credit: Ventana Medical Systems Inc. Licensed under CC BY-SA 4.0