FDA Approval Summary: Pembrolizumab, Atezolizumab, and Cemiplimab-rwlc as Single Agents for First-Line Treatment of Advanced/Metastatic PD-L1–High NSCLC
Oladimeji Akinboro, Erin Larkins, Lee H. Pai-Scherf, Luckson N. Mathieu, Yi Ren, Joyce Cheng, Mallorie H. Fiero, Wentao Fu, Youwei Bi, Shyam Kalavar, Samina Jafri, Pallavi S. Mishra-Kalyani, Jeanne Fourie Zirkelbach, Hongshan Li, Hong Zhao, Kun He, Whitney S. Helms, Meredith K. Chuk, Min Wang, Ilynn Bulatao, Jonathan Herz, Blaire L. Osborn, Yuan Xu, Jiang Liu, Yutao Gong, Sharon Sickafuse, Rebecca Cohen, Martha Donoghue, Richard Pazdur, Julia A. Beaver, Harpreet Singh
Abstract
FDA's approval of cemiplimab-rwlc on February 22, 2021, follows prior approvals of pembrolizumab and atezolizumab for similar indications as first-line treatment for patients with programmed death ligand-1 (PD-L1)-high advanced non-small cell lung cancer (NSCLC). Approvals of these anti-PD-L1 agents were supported by statistically significant and clinically meaningful improvements in overall survival (OS) in international, multicenter, active-controlled randomized trials. In KEYNOTE-024, the OS HR was 0.60 [95% confidence interval (CI), 0.41-0.89; P = 0.005] favoring pembrolizumab over platinum-doublet chemotherapy. In IMpower110, the OS HR was 0.59 (95% CI, 0.40-0.89; P = 0.0106) favoring atezolizumab over platinum-doublet chemotherapy. In Study 1624, the OS HR was 0.68 (95% CI, 0.53-0.87; P = 0.0022) favoring cemiplimab-rwlc over platinum-doublet chemotherapy. The progression-free survival (PFS) effect sizes for these anti-PD-L1 antibodies were also comparable across their respective registrational trials, and their safety profiles were consistent with the anti-PD-L1 class adverse event profile. The consistent survival benefits and manageable toxicity profiles of these single-agent anti-PD-L1 antibodies have established them as important treatment options in the PD-L1-high NSCLC treatment landscape. FDA approvals of these anti-PD-L1 antibodies, based on their favorable benefit-risk profiles, present effective chemotherapy-free therapeutic options for patients with advanced PD-L1-high NSCLC in the United States.