As reported in The Lancet by Ahmet Sezer, MD, of Başkent University, Adana, Turkey, and colleagues, 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 at least 50% of tumor cells (intended study population and as requested by the U.S. Food and Drug Administration [FDA]) and no EGFR, ALK, or ROS1 aberrations.¹ Cemiplimab was also associated with improved progression-free and overall survival in the intention-to-treat population.

Ahmet Sezer, MD

The study supported the February 2021 FDA approval of cemiplimab for the first-line treatment of patients with advanced ­NSCLC (locally advanced and not candidates for surgical resection or definitive chemoradiation or metastatic) whose tumors have high PD-L1 expression (tumor proportion score ≥ 50%) as determined by an 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 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 the 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). Randomization was stratified by tumor histology (squamous vs nonsquamous) and geographic region (Europe, Asia, or the rest of the world). 

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 at least 50% of tumor cells. The PD-L1 ≥ 50% population consisted of 283 patients in the cemiplimab group and 280 in the chemotherapy group.

Major Outcomes

In the intention-to-treat population, median follow-up was 13.1 months (interquartile range [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 of 203 patients (74%) whose disease progressed on chemotherapy crossed over to receive cemiplimab. A total of 50 of 158 patients (32%) whose disease progressed on cemiplimab received extended treatment with the addition of chemotherapy. Median overall survival was 22.1 months (95% confidence interval [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 (hazard ratio [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).

In the PD-L1 ≥ 50% population, median follow-up was 10.8 months (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% 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 (HR = 0.57, 95% CI = 0.42–0.77, P = .0002). Estimated rates at 24 months were 50% vs 27%. 

Hazard ratios for overall survival were in favor of cemiplimab in all subgroups examined, except among 94 female patients (1.11, 95% CI = 0.49–2.52). For stratification groups, hazard ratios were 0.48 (95% CI = 0.30–0.77) and 0.64 (95% CI = 0.43–0.96) for squamous and nonsquamous histologies and 0.54 (95% CI = 0.39–0.77), 0.76 (95% CI = 0.24–2.41), and 0.59 (95% CI = 0.26–1.33) for Europe, Asia, and the rest of the world.

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). Estimated rates at 12 months were 41% vs 7%. Hazard ratios favored cemiplimab in all subgroups examined. For stratification groups, hazard ratios were 0.48 (95% CI = 0.34–0.67) and 0.60 (95% CI = 0.44–0.81) for squamous and nonsquamous histologies and 0.50 (95% CI = 0.39–0.65), 0.70 (95% CI = 0.36–1.37), and 0.59 (95% CI = 0.30–1.14) for Europe, Asia, and the rest of world.

Adverse Events

Among patients who received at least one dose of assigned treatment, grade 3 to 4 adverse events occurred in 28% of the cemiplimab group vs 39% of the chemotherapy group; the most common events 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. Immune-mediated adverse events of any grade occurred in 17% of the cemiplimab group vs 2% of the chemotherapy group and were of grade ≥ 3 in 4% vs < 1%. 

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.” 

DISCLOSURE: The study was funded by Regeneron Pharmaceuticals and Sanofi. Dr. Sezer has received institutional honoraria from Amgen, Pfizer, and Roche; has participated in a speakers bureau for Amgen, Bristol Myers Squibb, Pfizer, and Roche; has received institutional research funding from Merck Serono, MSD Oncology, Novartis, Pfizer, and Regeneron; and has been reimbursed for travel, accommodations, and other expenses Amgen, Bristol Myers Squibb, and Roche.

REFERENCE

1. Sezer A, Kilickap S, Gümüş 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 397:592-604, 2021.