Merck announced the U.S FDA has approved Keytruda (pembrolizumab) as monotherapy for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (Combined Positive Score [CPS] ≥10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy. The FDA approval of Keytruda was based on the KEYNOTE-181 and KEYNOTE-180 clinical trials.
KEYNOTE-181 was a multi-center, randomized, open-label, active-controlled trial that enrolled 628 patients with recurrent locally advanced or metastatic esophageal cancer whose tumors express PD-L1 and who progressed on or after one prior line of systemic treatment for advanced disease. Patients were randomized (1:1) to receive either Keytruda 200 mg every three weeks or investigator’s choice of any of the following chemotherapy regimens, all given intravenously: paclitaxel 80-100 mg/m2 on Days 1, 8, and 15 of every four-week cycle, docetaxel 75 mg/m2 every three weeks, or irinotecan 180 mg/m2 every two weeks. Treatment with Keytruda or chemotherapy continued until unacceptable toxicity or disease progression. The trial met its primary endpoint of significantly improving overall survival (OS), with a 31% decrease in the risk of death compared to a chemotherapy regimen of paclitaxel, docetaxel or irinotecan.
KEYNOTE-180 was a multi-center, non-randomized, open-label trial that enrolled 121 patients with locally advanced or metastatic esophageal cancer who progressed on or after at least two prior systemic treatments for advanced disease. With the exception of the number of prior lines of treatment, the eligibility criteria were similar to and the dosage regimen identical to KEYNOTE-181. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DoR). The ORR in the 35 patients with ESCC expressing PD-L1 (CPS ≥10) was 20%. Among the seven responding patients, the DoR ranged from 4.2 to 25.1+ months, with five patients (71%) having responses of six months or longer and three patients (57%) having responses of 12 months or longer.
About Esophageal Cancer
Esophageal cancer is cancer that occurs in the esophagus—a long, hollow tube that runs from the back of the throat to the stomach. The esophagus helps move food from the back of the throat to the stomach to be digested.
Esophageal cancer usually begins in the cells that line the inside of the esophagus. Esophageal cancer can occur anywhere along the esophagus. More men than women get esophageal cancer.
Esophageal cancer is the sixth most common cause of cancer deaths worldwide.
Keytruda is a programmed death receptor-1 (PD-1)-blocking antibody. The immune system is your body’s natural defense against disease. The immune system sends certain types of cells called T cells throughout your body to detect and fight infections and diseases, including cancer. Cancer cells may use the PD-1 pathway to hide from T cells. This stops T cells from attacking cancer cells and allows cancer cells to grow and spread.