On July 30, 2019, the FDA approved pembrolizumab (Keytruda®, Merck) for patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus (ESCC) whose tumors expressed a programmed death-ligand 1 (PD-L1) combined positive score (CPS) of at least 10 and whose disease progressed after at least one line of systemic therapy. The approval was based on two clinical trials. One of these was Keynote-181, which enrolled 628 patients with locally advanced or metastatic ESCC who experienced disease progression after one systemic treatment and whose tumors expressed a PD-L1 CPS of at least 10; in this trial, pembrolizumab increased median overall survival compared with the control group (10.3 months vs 6.7 months). The second clinical trial, Keynote-180, enrolled 35 patients with locally advanced or metastatic ESCC whose disease progressed on or after at least two prior systemic treatments and whose cancer expressed a PD-L1 CPS of at least 10. In the Keynote-180 trial, pembrolizumab achieved an overall response rate of 20%, with response durations ranging from 4.2 to 25.1 months or more. Additionally, 71% of patients experienced responses of at least 6 months and 57% of patients experienced responses of at least 12 months. In this interview with i3 Health, Ken Kato, MD, PhD, the senior author of the Keynote-180 trial, discusses the significance of the approval and the future of treatment for advanced ESCC.
What is the significance of the approval of pembrolizumab for patients with advanced ESCC?
Ken Kato, MD, PhD: Of course, it is good news for ESCC patients.
How does pembrolizumab compare with other current treatments for advanced ESCC?
Dr. Kato: The comparator of pembrolizumab is taxanes [a drug class of diterpenes, a class of chemical compounds, used as chemotherapy agents]. As indicated in Keynote-181, the hematologic and non-hematologic toxicity of pembrolizumab is obviously low compared with that of the taxanes.
How do you foresee the treatment of advanced ESCC evolving, both in light of this approval and in the future?
Dr. Kato: Pembrolizumab monotherapy could be a new standard of care as second-line therapy for patients with ESCC whose CPS is at least 10. If pembrolizumab shows evidence of additional effectiveness over first-line chemotherapy, it would move to one of the first lines of standard care. Moreover, this has created a potential for developing immunotherapy for chemoradiotherapy or neoadjuvant therapy for advanced ESCC.
About Dr. Kato
Ken Kato, MD, PhD, is the Head of the Gastrointestinal Medical Oncology Division at the National Cancer Center Hospital in Tokyo, Japan, and the Group Coordinator of the Japanese Esophageal Oncology Group. His focus is on translational research on gastrointestinal cancer, especially ESCC.
For More Information
Clinicaltrials.gov (2019). Study of pembrolizumab (MK-3475) in previously-treated participants with advanced carcinoma of the esophagus or esophagogastric junction (MK-3475-180/Keynote-180). NLM identifier: NCT02559687.
Clinicaltrials.gov (2019). 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). NLM identifier: NCT02564263.
Kojima T, Muro K, Francois E, et al (2019). Pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer: Phase III KEYNOTE-181 study. J Clin Oncol. [Epub ahead of print] DOI:10.1200/JCO.2019.37.4_suppl.2Shah M, Kojima T, Hochhauser D, et al (2018). Efficacy and safety of pembrolizumab for heavily pretreated patients with advanced, metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: the phase 2 KEYNOTE-180 study. JAMA Oncology. [Epub ahead of print] DOI:10.1001/jamaoncol.2018.5441
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily represent those of i3 Health.