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.

• Authors: Takashi Kojima, Manish A Shah, Kei Muro, Eric Francois, Antoine Adenis, Chih-Hung Hsu, Toshihiko Doi, Toshikazu Moriwaki, Sung-Bae Kim, Se-Hoon Lee, Jaafar Bennouna, Ken Kato, Lin Shen, Peter Enzinger, Shu-Kui Qin, Paula Ferreira, Jia Chen, Gustavo Girotto, Christelle de la Fouchardiere, Helene Senellart, Raed Al-Rajabi, Florian Lordick, Ruixue Wang, Shailaja Suryawanshi, Pooja Bhagia, S Peter Kang, Jean-Philippe Metges, KEYNOTE-181 Investigators
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 38 Issue 35 Pg. 4138-4148 (12 10 2020) ISSN: 1527-7755 [Electronic] United States
• PMID: 33026938 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Immunological
• B7-H1 Antigen
• CD274 protein, human
• Docetaxel
• Irinotecan
• pembrolizumab
• Paclitaxel

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antineoplastic Agents, Immunological (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• B7-H1 Antigen (immunology)
• Docetaxel (administration & dosage)
• Esophageal Neoplasms (drug therapy, immunology, pathology)
• Esophageal Squamous Cell Carcinoma (drug therapy, immunology, pathology)
• Female
• Humans
• Irinotecan (administration & dosage)
• Male
• Middle Aged
• Paclitaxel (administration & dosage)
• Progression-Free Survival
• Survival Rate
• Young Adult