Pembrolizumab Regimen Approved for Advanced Gastroesophageal and Stomach Cancer
The FDA has approved a PD-1 blockade treatment regimen for certain patients with advanced stomach and gastroesophageal cancer.
The U.S. Food and Drug Administration (FDA) has granted traditional approval to pembrolizumab (Keytruda) in combination with trastuzumab (Herceptin) and chemotherapy for certain patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma that has not been previously treated and expresses human epidermal growth factor receptor 2 (HER2) and PD-L1.
This indication previously received an accelerated approval.
Pembrolizumab is a PD-1 immune checkpoint inhibitor, a type of immunotherapy that can enhance antitumor immune responses. Trastuzumab is an antibody that targets the HER2 protein overexpressed in many cancers. The chemotherapy regimen contains both fluoropyrimidine and platinum.
The conversion to a traditional approval was based on updated results from the multicenter, randomized, double-blind, placebo-controlled phase III KEYNOTE-811 trial. This study enrolled 698 patients with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma that had not been treated with systemic therapy. PD-L1-expression was observed in the tumors of 85% (594/698) of patients. All patients received trastuzumab plus chemotherapy, and were randomly assigned (1:1) to also receive either pembrolizumab or placebo.
Pembrolizumab treatment was associated with statistically significant increases in both survival and time until disease progression, an effect more pronounced in patients whose tumors expressed PD-L1. Compared with the placebo group, patients with PD-L1-positive tumors treated with pembrolizumab experienced a 28% reduction in risk of disease progression and a 21% reduction in risk of death during the study period, with half of patients in the pembrolizumab arm remaining progression-free at 10.9 months and half alive at 20.1 months. Seventy-three percent of tumors responded to the pembrolizumab regimen versus 58% to the control regimen.
The recommended dose of pembrolizumab is 200 mg every three weeks or 400 mg every six weeks, along with trastuzumab and chemotherapy.
Gastric or stomach cancer begins in the mucosal layer of the stomach and then spreads to cells in the outer linings. GEJ adenocarcinoma is a type of cancer that affects cells that produce mucus and starts in the area where the esophagus joins the stomach. According to federal statistics, it was estimated that there would be more than 30,000 individuals would be diagnosed with stomach cancer and approximately 10,780 would die of the disease in the United States in 2025.
The FDA rendered its decision on March 19, 2025. Check this resource for updated information on all therapeutics regulated by the FDA.