Pembrolizumab for Esophageal or Gastroesophageal Junction Carcinoma: Ken Kato, MD, PhD

Ken Kato, MD, PhD.

Recently, the FDA approved pembrolizumab (Keytruda®, Merck Sharp & Dohme Corp.) in combination with platinum/fluoropyrimidine-based chemotherapy for patients with metastatic or locally advanced esophageal or gastroesophageal junction (GEJ) carcinoma who do not qualify for surgical resection or definitive chemoradiation. The approval was based on the results of KEYNOTE-590, a phase 3 trial that demonstrated significant improvements in progression-free survival and overall survival for patients who were treated with pembrolizumab. In this interview, the principal investigator for KEYNOTE-590, Ken Kato, MD, PhD, of the National Cancer Center Hospital in Tokyo, Japan, speaks with Oncology Data Advisor about pembrolizumab for esophageal and GEJ carcinomas.

What are the most significant challenges of managing esophageal and GEJ carcinomas?

Ken Kato, MD, PhD: The median survival time for patients with esophageal and GEJ carcinomas is poor, less than 10-12 months, and there were only a few treatment options for decades. There was no standard of care with robust evidence for first-line chemotherapy of esophageal cancer, and the regimen was varied. This is the first time that a phase 3 trial has shown positive results for first-line chemotherapy of esophageal cancer. The results of KEYNOTE-590 may encourage further clinical development for esophageal cancer.

Can you comment on the significance of the results of KEYNOTE-590?

Dr. Kato: I would like to emphasize that KEYNOTE-590 showed the positive effects of pembrolizumab in a population with a combined-positive score of at least 10. In addition, the early drop of the progression-free survival curve was smaller for immuno-oncology combined with chemotherapy, compared with immuno-oncology monotherapy. This is the first time to exceed the median survival time of one year for patients with esophageal cancer.

What adverse events are of particular concern with this treatment regimen, and how are these best managed?

Dr. Kato: The combination of pembrolizumab with chemotherapy increases the toxicity, but the magnitude is small and manageable. We have experienced immune-related adverse events in the second-line treatment with immuno-oncology monotherapy, so the immune-related adverse events of chemotherapy with pembrolizumab are not an issue in clinical practice.

How do you see the treatment of esophageal and GEJ carcinomas evolving in light of this approval?

Dr. Kato: I hope more clinical trials will be conducted based on the results of KEYNOTE-590. Already, a new trial combining immuno-oncology with an anti-angiogenesis tyrosine kinase inhibitor has been conducted. Also, a trial of perioperative chemotherapy or chemoradiotherapy in combination with immuno-oncology has started. From that point of view, this approval would be the milestone of the esophageal cancer treatment.

About Dr. Kato

Ken Kato, MD, PhD, is the Chief of the Department of Esophageal, Head, and Neck Medical Oncology 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 esophageal squamous cell carcinoma.

For More information

Clinicaltrials.gov (2020). First-line esophageal carcinoma study with chemo vs. chemo plus pembrolizumab (MK-3475-590/KEYNOTE-590). NLM identifier: NCT03189719.

Transcript edited for clarity. Any views expressed above are the speaker’s own and do not necessarily reflect those of Oncology Data Advisor.


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