Study of Pembrolizumab (MK-3475) Versus Investigator's Choice Standard Therapy for Participants With Advanced Esophageal/ Esophagogastric Junction Carcinoma That Progressed After First-Line Therapy (MK-3475-181/KEYNOTE-181)
Summary
In this study, participants with advanced or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the esophagogastric junction (EGJ) that had progressed after first-line standard therapy were randomized to receive either pembrolizumab (MK-3475) OR the Investigator's choice of standard chemotherapy with paclitaxel, docetaxel, or irinotecan. The primary study hypothesis was that treatment with pembrolizumab would prolong overall survival (OS) as compared to treatment with standard chemotherapy.
Timeline
- Start
- 2015-12-01
- Primary completion
- 2018-10-15
- Completion
- 2022-03-14
Outcome
Mixed primary results
registry analysis (superiority test); Pembrolizumab vs Chemotherapy; p = 0.00894; Hazard Ratio (HR) 0.77 (95% CI 0.63 to 0.96) NCT02564263 ↗
registry analysis (superiority test); Pembrolizumab vs Chemotherapy; p = 0.00855; Hazard Ratio (HR) 0.70 (95% CI 0.52 to 0.94) NCT02564263 ↗
registry analysis (superiority test); Pembrolizumab vs Chemotherapy; p = 0.0531; Hazard Ratio (HR) 0.89 (95% CI 0.75 to 1.05) NCT02564263 ↗
Publications
- Results Kojima T, Shah MA, Muro K, Francois E, Adenis A, Hsu CH, Doi T, Moriwaki T, Kim SB, Lee SH, Bennouna J, Kato K, Shen L, Enzinger P, Qin SK, Ferreira P, Chen J, Girotto G, de la Fouchardiere C, Senellart H, Al-Rajabi R, Lordick F, Wang R, Suryawanshi S, Bhagia P, Kang SP, Metges JP; KEYNOTE-181 Investigators. Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer. J Clin Oncol. 2020 Dec 10;38(35):4138-4148. doi: 10.1200/JCO.20.01888. Epub 2020 Oct 7.
- Adenis A, Kulkarni AS, Girotto GC, de la Fouchardiere C, Senellart H, van Laarhoven HWM, Mansoor W, Al-Rajabi R, Norquist J, Amonkar M, Suryawanshi S, Bhagia P, Metges JP. Impact of Pembrolizumab Versus Chemotherapy as Second-Line Therapy for Advanced Esophageal Cancer on Health-Related Quality of Life in KEYNOTE-181. J Clin Oncol. 2022 Feb 1;40(4):382-391. doi: 10.1200/JCO.21.00601. Epub 2021 Nov 3.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Docetaxel | Small molecule | 75 mg/m2 | Intravenous |
| Comparator | Irinotecan | Small molecule | 180 mg/m2 | Intravenous |
| Comparator | Paclitaxel | Small molecule | 80 mg/m2 | Intravenous |
| Comparator | Paclitaxel | Small molecule | 100 mg/m2 | Intravenous |
| Subject | Pembrolizumab | Monoclonal antibody | 200 mg | Intravenous |