As reported in The Lancet by Sezer et al, the phase III EMPOWER-Lung 1 trial has shown improved overall and progression-free survival with cemiplimab-rwlc vs platinum doublet chemotherapy among patients with advanced non–small cell lung cancer (NSCLC) with PD-L1 expression on ≥ 50% of tumor cells and no EGFR, ALK, or ROS1 aberrations.

The study supported the February 2021 approval of cemiplimab-rwlc for the first-line treatment of patients with advanced NSCLC (those with locally advanced disease as well as those who are not candidates for surgical resection or definitive chemoradiation or metastatic) with tumors that have high PD-L1 expression (tumor proportion score > 50%) as determined by a U.S. Food and Drug Administration (FDA)-approved test and no EGFR, ALK. or ROS1 aberrations.

Study Details

In the open-label trial, 710 patients with stage IIIB to IV squamous or nonsquamous NSCLC with PD-L1 ≥ 50% from sites in 24 countries were randomly assigned between June 2017 and February 2020 to receive  cemiplimab at 350 mg intravenously every 3 weeks for up to 108 weeks  (n = 356) or four to six cycles of investigator’s choice of platinum-doublet chemotherapy (n = 354). The most common chemotherapy regimens selected were paclitaxel plus carboplatin (n = 127), pemetrexed plus carboplatin (n = 98), and  gemcitabine plus carboplatin (n = 40). Never-smokers were not eligible for the trial.

Crossover from chemotherapy to cemiplimab was permitted following disease progression. The primary endpoints were overall survival and progression-free survival on independent review committee assessment, with the endpoints being evaluated in the intention-to-treat population and in a prespecified population of patients with PD-L1 expression in ≥ 50% of tumor cells on the 22C3 assay performed according to instructions for use (per FDA request). This PD-L1 ≥ 50% population consisted of 283 patients in the cemiplimab group and 280 in the chemotherapy group.

Overall and Progression-Free Survival

In the PD-L1 ≥ 50% population, median follow-up was 10.8 months (interquartile range [IQR] = 7.6–15.8 months) in the cemiplimab group and 10.9 months (IQR = 7.8–15.6 months) in the chemotherapy group. Median overall survival was not reached (95% confidence interval [CI] = 17.9 months to not evaluable) in the cemiplimab group vs 14.2 months (95% CI = 11.2–17.5 months) in the chemotherapy group (hazard ratio [HR] = 0.57, 95% CI = 0.42–0.77, P = .0002). Median progression-free survival was 8.2 months (95% CI = 6.1–8.8 months) with cemiplimab vs 5.7 months (95% CI = 4.5–6.2 months) with chemotherapy (HR = 0.54, 95% CI = 0.43–0.68, P < .0001). Objective response rates were 39% vs 20%, and median response durations were 16.7 months (95% CI = 12.5–22.8 months) vs 6.0 months (95% CI = 4.3–6.5 months).

In the intention-to-treat population, median follow-up was 13.1 months (IQR = 8.6–20.2 months) in the cemiplimab group and 13.1 months (IQR = 8.7–20.1 months) in the chemotherapy group. A total of 150 (74%) of 203 patients who had disease progression on chemotherapy crossed over to receive cemiplimab.

Median overall survival was 22.1 months (95% CI = 17.7 months to not evaluable) in the cemiplimab group vs 14.3 months (95% CI = 11.7–19.2 months) in the chemotherapy group (HR = 0.68, 95% CI = 0.53–0.87, P = .0022). Median  progression-free survival was 6.2 months (95% CI = 4.5–8.3 months) vs 5.6 months (95% CI = 4.5–6.1 months; HR = 0.59, 95% CI =  0.49–0.72, P < .0001).

Adverse Events

Grade 3 or 4 adverse events occurred in 28% of the cemiplimab group vs 39% of the chemotherapy group; the most common were pneumonia (5%), anemia (3%), and hyponatremia (3%) in the cemiplimab group and anemia (16%), neutropenia (10%), and thrombocytopenia (8%) in the chemotherapy group. Serious adverse events occurred in 28% vs 27% of patients.

Adverse events led to discontinuation of treatment in 6% vs 4%. Death considered related to treatment occurred in nine patients (3%) in the cemiplimab group, with causes consisting of autoimmune myocarditis, cardiac failure, cardiopulmonary failure, cardiorespiratory arrest, nephritis, respiratory failure, septic shock, tumor hyperprogression, and unknown cause in one patient each. Treatment-related death occurred in seven patients (2%) in the chemotherapy group, with causes consisting of pneumonia and pulmonary embolism in two patients each and cardiac arrest, lung abscess, and myocardial infarction in one patient each.

The investigators concluded: “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.”

Ahmet Sezer, MD, Department of Medical Oncology, Başkent University, Adana, Turkey, is the corresponding author for The Lancet article.

Disclosure: The study was funded by Regeneron Pharmaceuticals and Sanofi. For full disclosures of the study authors, visit thelancet.com.