FDA Approves Cemiplimab for Frontline Advanced NSCLC With High PD-L1 Expression


February 22, 2021 - The FDA has approved cemiplimab-rwlc monotherapy for use in the frontline treatment of patients with advanced non–small cell lung cancer with a PD-L1 expression level of 50% or higher.



The FDA has approved cemiplimab-rwlc (Libtayo) monotherapy for use in the frontline treatment of patients with advanced non–small cell lung cancer (NSCLC) with a PD-L1 expression level of 50% or higher.1

The decision was based on data from an analysis of 710 patients with a PD-L1 expression of 50% or higher who had been randomized to receive the agent in the phase 3 EMPOWER-Lung 1 trial (NCT033088540). In this population, cemiplimab reduced the risk of death by 32% versus chemotherapy. The median overall survival (OS) with cemiplimab was 22 months versus 14 months with chemotherapy (HR, 0.68; 95% CI, 0.53-0.87; P = .0022).2

Cemiplimab was also found to improve progression-free survival (PFS) over chemotherapy. The median PFS in the investigational arm was 6.2 months (95% CI, 4.5-8.3) per blinded independent central compared with 5.6 months (95% CI, 4.5-6.1) in the control arm (HR, 0.59; 95% CI, 0.49-0.72; P <.0001).

“The approval of [cemiplimab] to treat first-line advanced NSCLC with high PD-L1 expression means physicians and patients have a potent new treatment option against this deadly disease,” said Naiyer Rizvi, MD, Price Family Professor of Medicine, director of Thoracic Oncology and co-director of Cancer Immunotherapy at Columbia University Irving Medical Center, as well as a steering committee member of the trial, stated in a press release.

“Notably, [cemiplimab] was approved based on a pivotal trial where most chemotherapy patients crossed over to [cemiplimab] following disease progression, and that allowed for frequently underrepresented patients who had pretreated and clinically stable brain metastases, or who had locally advanced disease and were not candidates for definitive chemoradiation," added Rizvi. "This gives doctors important new data when considering [cemiplimab] for the varied patients and situations they treat in daily clinical practice.”

The multicenter, open-label, global, phase 3 trial evaluated cemiplimab monotherapy compared with investigator’s choice of platinum-doublet chemotherapy in the first-line treatment of patients with advanced NSCLC whose tumors have a PD-L1 expression of 50% or higher.

To be eligible for enrollment, patients had to be 18 years of age, have histologically or cytologically confirmed stage IIIB or IIIC or stage IV squamous or nonsquamous disease with PD-L1 expression of at least 50%, an ECOG performance status of 0-1, adequate organ and bone marrow function, and at least 1 measurable lesion per RECIST v1.1 criteria.

If patients had never smoked; had active or untreated brain metastases; had tumors that harborded EGFR mutations, ALK translocations, or ROS1 fusions; had active, known, or suspected autoimmune disease that called for systemic therapy during the previous 2 years; or had uncontrolled infection with hepatitis B or C or human immunodeficiency virus, they were excluded from the research.

Patients were stratified based on histology (squamous vs nonsquamous) and geographical region (Europe, Asia, or the rest of the world). Participants received either 350 mg of intravenous cemiplimab over 30 minutes every 3 weeks (n = 356) or investigator’s choice of platinum-based chemotherapy for 4 or 6 cycles (n = 354).

The primary end points of the trial were OS and PFS, while secondary end points comprised objective response rate (ORR), duration of response (DOR), health-related quality of life (HRQoL), and safety with cemiplimab versus chemotherapy. Moreover, investigators examined the pharmacokinetics and immunogenicity of cemiplimab and conducted exposure–response analyses.

Additional results showed that 39% of patients who received cemiplimab achieved an objective response per independent review committee compared with 20% of those who received chemotherapy. The median DOR experienced with cemiplimab was 16.7 months versus 6.0 months with chemotherapy.

Results from an additional prespecified analysis conducted in 563 patients with proven PD-L1 expression of at least 50% showed that cemiplimab reduced the risk of death by 43% versus chemotherapy. Here, the median OS had not yet been reached in the investigative arm versus 14 months in the control arm (HR, 0.57; 95% CI, 0.42-0.77; P = .0002). Moreover, the median PFS was 8 months and 6 months with cemiplimab and chemotherapy, respectively (HR, 0.54; 95% CI, 0.433-0.68; P <.0001).

Safety was evaluated in a total of 355 patients in the cemiplimab arm and 342 patients in the chemotherapy arm. Toxicities that were more frequently reported in the cemiplimab arm over the chemotherapy arm included rash (15% vs 6%, respectively) and cough (11% vs 8%). The most common serious adverse effects included pneumonia (5% vs 6%) and pneumonitis (2% vs 0%).

Six percent of patients discontinued treatment with cemiplimab because of toxicities such as pneumonitis, pneumonia ischemic stroke, and increased aspartate aminotransferase (at least 2 patients).


  1. FDA approves Libtayo (cemiplimab-rwlc) monotherapy for patients with first-line advanced non–small cell lung cancer with PD-L1 expression of ≥50%. News release. Sanofi. February 22, 2021. Accessed February 22, 2021. http://bit.ly/2MekSFT
  2. Sezer A, Kilickap S, Gümüs M, et al. 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. 2021;397(10274):592-604. doi:10.1016/S0140-6736(21)00228-2
Related Videos
Jonathan Wesley Riess, MD, MS, an associate professor at the University of California (UC) Davis
Joachim G. J. V. Aerts, MD, PhD
Alessandro Di Federico, MD
Expert on SCLC
Dazhi Liu, PharmD, MS, BCOP
Stephen V. Liu, MD
Sanam Loghavi, MD
Experts on lung cancer
Luis Raez, MD, an expert on lung cancer
Jia Luo, MD
Related Content