The Food and Drug Administration (FDA) has approved Keytruda (pembrolizumab; Merck) for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test, with disease progression after 1 or more prior lines of systemic therapy.

The approval was based on data from the KEYNOTE-181 study which included 628 patients with recurrent locally advanced or metastatic esophageal cancer who progressed on or after 1 prior line of systemic treatment for advanced disease. Patients were randomized to receive Keytruda 200mg every 3 weeks or investigator’s choice of IV chemotherapy (paclitaxel 80-100mg/m2 on Days 1, 8, and 15 of every 4-week cycle, docetaxel 75mg/m2 every 3 weeks, or irinotecan 180mg/m2 every 2 weeks); randomization was stratified by tumor histology (esophageal squamous cell carcinoma [ESCC] vs esophageal adenocarcinoma [EAC]/Siewert type I EAC of the gastroesophageal junction [GEJ]), and geographic region (Asia vs ex-Asia). The primary efficacy outcome of the study was overall survival.

Results showed the observed overall survival hazard ratio (HR) was 0.77 (95% CI: 0.63 to 0.96) in patients with ESCC, 0.70 (95% CI: 0.52 to 0.94) in patients with tumors expressing PD-L1 (CPS ≥10), and 0.89 (95% CI: 0.75 to 1.05) in all randomized patients. Among patients whose ESCC tumors expressed PD-L1 (CPS ≥10) (n=167), median overall survival in the Keytruda arm was 10.3 months (95% CI: 7.0 to 13.5) vs 6.7 months in the chemotherapy arm (95% CI: 4.8 to 8.6) (HR 0.64 [95% CI: 0.46 to 0.90]).

The indication was also supported by data from KEYNOTE-180 (N=120), a nonrandomized, open label trial, in which overall response rate and duration of response were the co-primary end points. Results showed that the objective response rate in the 35 patients with ESCC expressing PD-L1 was 20% (95% CI: 8 to 37). Duration of response ranged from 4.2 to 25.1+ months among the 7 responding patients; 5 patients had responses of ≥6 months and 3 patients had responses of ≥12 months.

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“Historically, patients with advanced esophageal cancer have had limited treatment options, particularly after their disease has progressed,” said Dr Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories. “With this approval, Keytruda is now the first anti-PD-1 therapy approved for the treatment of previously-treated patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS ≥10), providing an important new monotherapy option for physicians and patients in the United States.”

Keytruda, a programmed death receptor-1 (PD-1)-blocking antibody, is also indicated for the treatment of small cell lung cancer, non-small cell lung cancer, melanoma, head and neck squamous cell cancer, classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, urothelial carcinoma, microsatellite instability-high cancer, gastric cancer, cervical cancer, hepatocellular carcinoma, merkel cell carcinoma, and renal cell carcinoma.

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