Keytruda Promising in PD-L1 Esophageal Cancer
by C.H. Weaver M.D. (08/2018)
The checkpoint inhibitor Keytruda (pembrolizumab) has been reported to produce an overall response rate of 30% in patients with PD-L1–positive, advanced esophageal cancer.1
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.
KEYNOTE-028 is a clinical trail that evaluated keytruda in patients with 20 different types of PD-L1–positive advanced solid tumors. PD-L1–positive, squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction for which standard therapy did not exist or was ineffective.
For the 23 patients enrolled in the study the 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 malignancies, the authors noted. 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.
- Doi T, et al “Safety and antitumor activity of the anti–programmed death-1 antibody pembrolizumab in patients with advanced esophageal carcinoma” J Clin Oncol 2018; DOI: 10.1200/JCO.2017. 74.9846.
- 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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