FDA Approves Cemiplimab Plus Chemo in Advanced NSCLC

Based on results of the phase 3 EMPOWER-Lung3 trial, frontline use of cemiplimab plus chemotherapy has been approved by the FDA for patients with advanced non–small cell lung cancer.

The FDA has approved cemiplimab-rwlc (Libtayo) plus platinum-based chemotherapy as first-line therapy in patients with advanced non–small cell lung cancer (NSCLC) who lack EGFR, ALK, or ROS1 mutations, according to a recent press release.1 

The approval was based on results from the phase 3 EMPOWER-Lung 3 trial (NCT03409614) in which patients with advanced NSCLC were given cemiplimab plus chemotherapy or placebo plus chemotherapy.2 The median overall survival (OS) was 21.9 months (95% CI, 15.5-not evaluable [NE]) in the cemiplimab arm vs 13.0 months (95% CI, 11.9-16.1) in the placebo arm (HR, 0.71; 95% CI, 0.53-0.93; P = .014).

“Clearly, this is an advance which is clinically meaningful for our patients with advanced stage non-small cell lung cancer,” David R. Gandara, MD, professor emeritus and senior advisor of the Thoracic Oncology Program at the University of California Davis Comprehensive Cancer Center, said in the press release.

A total of 466 patients were randomly assigned 2:1 with 312 in the cemiplimab-plus-chemotherapy arm vs 154 in the placebo arm. Overall, 42.9% of patients had squamous histology, 84.3% had an ECOG performance status of 1, and 14.8% had locally advanced disease.

Based on a recommendation from the independent data monitoring committee, the trial was stopped early due to the preset criteria for overall survival (OS) superiority being met. At data cutoff, 108 patients in the combination arm and 15 in the chemotherapy arm were still receiving treatment. Treatment discontinuation occurred due to progressive disease in 65.4% of patients receiving the combination treatment compared with 89.6% in the placebo arm. In each corresponding arm, the median duration of follow-up was 16.3 months and 16.7 months.

The proportion of patients alive at 12 months in the combination arm was 65.7% (95% CI, 59.9%-70.9%) vs 56.1% (95% CI, 47.5%-63.8%) in the placebo arm.

In patients who had squamous histology, the median OS was 21.9 months (95% CI, 15.6-NE) with cemiplimab vs 13.8 months (95% CI, 9.3-18.0; HR 0.56; 95% CI, 0.37-0.84) with placebo. In the nonsquamous histology subgroup, the median OS was 15.8 months (95% CI, 13.7-NE) vs 13.0 months (95% CI, 10.0-NE; HR, 0.79; 95% CI, 0.54-1.14) in the combination and placebo arms, respectively.

The median progression-free survival in the cemiplimab plus chemotherapy arm was 8.2 months (95% CI, 6.4-9.3) vs 5.0 months (95% CI, 4.3-6.2) in the placebo arm (HR, 0.56; 95% CI, 0.44-0.70; P <.0001). Those who were alive and disease free at 12 months comprised 38.1% (95% CI, 32.4%-43.8%) of patients in the combination arm vs 16.4% (95% CI, 10.5%-23.4%) in the placebo arm.

The overall response rate (ORR) was 43.3% (95% CI, 37.7%-49.0%) in the cemiplimab plus chemotherapy arm with a complete response rate of 2.6% and a partial response (PR) rate of 40.7%. In the placebo arm, the ORR was 22.7% (95% CI, 16.4%-30.2%) with all responses being PRs. In the combination arm, the median duration of response was 15.6 months (95% CI, 12.4-NE) vs 7.3 months (95% CI, 4.3-12.6) in the placebo arm.

Patients were exposed to treatment for a median of 38.5 weeks in the combination arm and 21.3 weeks in the placebo arm. Treatment-emergent adverse effects (TEAEs) occurred in 95.8% of patients in the combination arm, with 43.6% experiencing grade 3 or higher events. The most common TEAEs that occurred at grade 3 or higher were anemia (9.9%) and neutropenia (5.8%). In the placebo arm, TEAEs occurred in 94.1% of patients with 31.4% being grade 3 or higher. The most common grade 3 or higher TEAEs were anemia (6.5%) and neutropenia (5.9%).

Treatment discontinuation because of TEAEs occurred in 5.1% of patients in the combination arm and 2.6% in the placebo arm. TEAEs led to death between in 6.1% vs 7.8% of patients, respectively.

Treatment-related AEs occurred in 88.1% of patients in the combination arm and 84.3% in the placebo arm. Immune-related AEs were observed in 18.9% of patients in the cemiplimab arm, with grade 3 or higher immune-related AEs occurring in 2.9%. Discontinuation due to immune-related AEs happened in 1.0% of patients, with 0.3% dying from immune-mediated pneumonitis.


  1. FDA approves cemiplimab-rwlc in combination with platinum-based chemotherapy for non-small cell lung cancer. News release. FDA. November 8, 2022. Accessed November 9, 2022. https://bit.ly/3WO0BX1
  2. Gogishvili M, Melkadze T, Makharadze T, et al. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial. Nat Med. Published online August 25, 2022. doi:10.1038/s41591-022-01977-y