by C.H. Weaver M.D. updated 1/2019
The checkpoint inhibitor Keytruda (pembrolizumab) was initially reported to produce an overall response rate of 30% in patients with PD-L1–positive, advanced esophageal cancer.(1) Additional results from the Keynote 181 clinical trial confirmed that Keytruda reduces the risk of death by 31% compared to treatment with chemotherapy in patients with esophageal or esophagogastric junction cancer or adenocarcinoma of the esophagus who progressed after initial standard chemotherapy.
Keytruda is a monoclonal antibody that helps to restore the body’s immune system in fighting cancer. It creates its anti-cancer effects by blocking a specific protein used by cancer cells called the programmed death-ligand 1 (PD-L1), to escape an attack by the immune system. Once PD-L1 is blocked, cells of the immune system are able to identify cancer cells as a threat and initiate an attack to destroy the cancer.
About Esophageal Cancer
The esophagus is a muscular tube that food and liquids pass through on their on their way to the stomach. Each year in the United States, more than 17,000 people are diagnosed with cancer of the esophagus and more than 15,000 die of the disease.2 Although many people with esophageal cancer are diagnosed with advanced disease, treatment has slowly improved, and survival rates are getting better. During the 1960s and 1970s, only about 5% of patients survived 5 years after being diagnosed. Now, about 20% of patients survive at least 5 years. The high death rate associated with esophageal cancer is largely attributed to the fact that the disease is often diagnosed once it has already become advanced, and few good treatment options exist. There is a very substantial unmet need for effective and well-tolerated treatments for patients with advanced esophageal carcinoma.
The KEYNOTE-028 clinical trial initially evaluated Keytruda in patients with 20 different types of PD-L1–positive advanced solid tumors. For the 23 patients enrolled in the study with esophageal cancer their overall response to treatment was 30%; all seven responses were confirmed partial responses. For patients with squamous cell carcinoma the rate was 28%, and for those with adenocarcinoma it was 40%. The overall safety profile in the study was similar to that previously reported for Keytruda in patients with other advanced cancers. Similar to the results from other studies of immune checkpoint inhibition in cancer, only a subset of patients with PDL1–positive esophageal cancer showed a clinical benefit from PD-1 blockade, suggesting that additional biomarkers could help predict clinical response.
In order to confirm the encouraging results with Keytruda in Keynote-028 the phase 3 Keynote-181 clinical trial was designed to assess Keytruda monotherapy in the second-line treatment of advanced or metastatic esophageal or esophagogastric junction carcinoma.
Keynote 181 directly compared Keytruda to chemotherapy in ~ 600 individuals with esophageal cancer that had recurred after initial chemotherapy treatment which consisted of the investigator’s choice of chemotherapy including Taxotere (docetaxel), Taxol (paclitaxel) or Camptosar (irinotecan).
American Cancer Society. Cancer Facts and Figures 2015. Available at http://www.cancer.org/acs/groups/content/@research/documents/webcontent/acspc-042151.pdf. Accessed March 16, 2015.
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