Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer - PubMed (original) (raw)

Clinical Trial

. 2020 Dec 10;38(35):4138-4148.

doi: 10.1200/JCO.20.01888. Epub 2020 Oct 7.

Manish A Shah 2, Kei Muro 3, Eric Francois 4, Antoine Adenis 5, Chih-Hung Hsu 6, Toshihiko Doi 7, Toshikazu Moriwaki 8, Sung-Bae Kim 9, Se-Hoon Lee 10, Jaafar Bennouna 11, Ken Kato 12, Lin Shen 13, Peter Enzinger 14, Shu-Kui Qin 15, Paula Ferreira 16, Jia Chen 17, Gustavo Girotto 18, Christelle de la Fouchardiere 19, Helene Senellart 20, Raed Al-Rajabi 21, Florian Lordick 22, Ruixue Wang 23, Shailaja Suryawanshi 23, Pooja Bhagia 23, S Peter Kang 23, Jean-Philippe Metges 24; KEYNOTE-181 Investigators

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Clinical Trial

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

Takashi Kojima et al. J Clin Oncol. 2020.

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.

Trial registration: ClinicalTrials.gov NCT02564263.

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