Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer

Abstract

PURPOSE Patients with advanced esophageal cancer have a poor prognosis and limited treatment options after first-line chemotherapy. PATIENTS AND METHODS In this open-label, phase III study, we randomly assigned (1:1) 628 patients with advanced/metastatic squamous cell carcinoma or adenocarcinoma of the esophagus, that progressed after one prior therapy, to pembrolizumab 200 mg every 3 weeks for up to 2 years or chemotherapy (investigator’s choice of paclitaxel, docetaxel, or irinotecan). Primary end points were overall survival (OS) in patients with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 10, in patients with squamous cell carcinoma, and in all patients (one-sided α 0.9%, 0.8%, and 0.8%, respectively). RESULTS At final analysis, conducted 16 months after the last patient was randomly assigned, OS was prolonged with pembrolizumab versus chemotherapy for patients with CPS ≥ 10 (median, 9.3 v 6.7 months; hazard ratio [HR], 0.69 [95% CI, 0.52 to 0.93]; P = .0074). Estimated 12-month OS rate was 43% (95% CI, 33.5% to 52.1%) with pembrolizumab versus 20% (95% CI, 13.5% to 28.3%) with chemotherapy. Median OS was 8.2 months versus 7.1 months (HR, 0.78 [95% CI, 0.63 to 0.96]; P = .0095) in patients with squamous cell carcinoma and 7.1 months versus 7.1 months (HR, 0.89 [95% CI, 0.75 to 1.05]; P = .0560) in all patients. Grade 3-5 treatment-related adverse events occurred in 18.2% of patients with pembrolizumab versus 40.9% in those who underwent chemotherapy. CONCLUSION Pembrolizumab prolonged OS versus chemotherapy as second-line therapy for advanced esophageal cancer in patients with PD-L1 CPS ≥ 10, with fewer treatment-related adverse events.

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Affiliated Institutions

• Aichi Cancer Center JP
• Harvard University US
• Hospital de Base BR
• Jiangsu Cancer Hospital CN
• Merck & Co., Inc., Rahway, NJ, USA (United States) US
• Université de Montpellier FR
• Samsung Medical Center KR
• Tokyo National Hospital JP
• University Cancer Center Hamburg DE
• Peking University CN
• IPO Porto PT
• Centre Léon Bérard FR
• Inserm FR
• Institut de Cancérologie de l'Ouest FR
• Centre Antoine Lacassagne FR
• Peking University Cancer Hospital CN
• Institut Génétique Nantes Atlantique FR
• The University of Kansas Cancer Center US
• Dana-Farber Cancer Institute US
• University of Tsukuba Hospital JP
• Centre Hospitalier Régional Universitaire de Brest FR
• National Cancer Center Hospital East JP
• Cornell University US
• 81th Hospital of PLA CN
• National Taiwan University Hospital TW
• Asan Medical Center KR

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