Takashi Kojima1, Manish A Shah2, Kei Muro3, Eric Francois4, Antoine Adenis5, Chih-Hung Hsu6, Toshihiko Doi7, Toshikazu Moriwaki8, Sung-Bae Kim9, Se-Hoon Lee10, Jaafar Bennouna11, Ken Kato12, Lin Shen13, Peter Enzinger14, Shu-Kui Qin15, Paula Ferreira16, Jia Chen17, Gustavo Girotto18, Christelle de la Fouchardiere19, Helene Senellart20, Raed Al-Rajabi21, Florian Lordick22, Ruixue Wang23, Shailaja Suryawanshi23, Pooja Bhagia23, S Peter Kang23, Jean-Philippe Metges24. 1. National Cancer Center Hospital East, Kashiwa, Japan. 2. Weill Cornell Medical College, New York, NY. 3. Aichi Cancer Center Hospital, Nagoya, Japan. 4. CLCC Antoine Lacassagne, Nice, France. 5. IRCM, Inserm, Université Montpellier, ICM, Montpellier, France. 6. National Taiwan University Hospital, Taipei, Taiwan. 7. National Cancer Center Hospital East, Chiba, Japan. 8. University of Tsukuba Hospital, Tsukuba, Japan. 9. Asan Medical Center, Seoul, South Korea. 10. Samsung Medical Center, Seoul, South Korea. 11. Institut de Cancerologie de L'Ouest, Nantes, France. 12. National Cancer Center Hospital, Tokyo, Japan. 13. Beijing Cancer Hospital, Beijing, China. 14. Dana Farber Cancer Institute and Harvard Medical School, Boston, MA. 15. PLA Cancer Centre of Nanjing Bayi Hospital, Nanjing, China. 16. Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E., Porto, Portugal. 17. Jiangsu Cancer Hospital, Nanging, China. 18. Hospital de Base de Sao Jose do Rio Preto, Sao Jose do Rio Preto, Brazil. 19. Centre Leon Berard, Lyon, France. 20. Centre Rene Gauducheau ICO, Saint Herblain, France. 21. University of Kansas Cancer Center, Westwood, KS. 22. University Cancer Center Leipzig, Leipzig, Germany. 23. Merck & Co, Inc, Kenilworth, NJ. 24. CHU Brest - Institut de Cancerologie et d'Hematologie, Arpego Network, Brest, France.
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, topembrolizumab 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.
RCT Entities:
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: Daniel V T Catenacci; Stephanie Moya; Samantha Lomnicki; Leah M Chase; Bryan F Peterson; Natalie Reizine; Lindsay Alpert; Namrata Setia; Shu-Yuan Xiao; John Hart; Uzma D Siddiqui; D Kyle Hogarth; Oliver S Eng; Kiran Turaga; Kevin Roggin; Mitchell C Posner; Paul Chang; Sunil Narula; Murtuza Rampurwala; Yuan Ji; Theodore Karrison; Chih-Yi Liao; Blase N Polite; Hedy L Kindler Journal: Cancer Discov Date: 2020-11-24 Impact factor: 39.397
Authors: Salma K Jabbour; Terence M Williams; Mutlay Sayan; Eric D Miller; Jaffer A Ajani; Andrew C Chang; Norman Coleman; Wael El-Rifai; Michael Haddock; David Ilson; Daniel Jamorabo; Charles Kunos; Steven Lin; Geoffrey Liu; Pataje G Prasanna; Anil K Rustgi; Rosemary Wong; Bhadrasain Vikram; Mansoor M Ahmed Journal: J Natl Cancer Inst Date: 2021-06-01 Impact factor: 13.506