The U.S. Food and Drug Administration (FDA) announced approval of Bristol-Myers Squibb's (BMS) blockbuster PD-1 inhibitor Opdivo (nivolumab) in combination with chemotherapy as a first-line treatment for advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, and esophageal adenocarcinoma. It is the first FDA-approved immunotherapy for first-line gastric cancer.
Stomach cancer is the fifth most common cancer and the third leading cause of cancer death worldwide. Gastric cancer is the second most common cancer in China after lung cancer. It accounts for 44 percent of cases and 50 percent of deaths worldwide. Eighty percent of Chinese patients with gastric cancer are already in advanced stages when they are diagnosed. For the majority of patients with advanced gastric cancer, chemotherapy has remained the first choice of first-line treatment in the past decades. However, the efficacy of chemotherapy is limited, with a 5-year survival rate of only 5% in patients with advanced or metastatic gastric cancer.
Opdivo, developed by Bristol-Myers Squibb, is a monoclonal antibody that targets PD-1. It enhances the anti-cancer immune response of T lymphocytes by inhibiting the PD-1 immune checkpoint protein-mediated signaling pathway, thereby inhibiting tumor growth. Since it was first approved by the FDA in 2014, it has been approved in more than 65 countries and territories around the world to treat a variety of cancer types, including melanoma and non-small cell lung cancer.
This approval was supported by a randomized, open-label phase 3 clinical trial called CHECKMATE -649. A total of 1581 untreated patients with advanced or metastatic gastric, GEJ, and esophageal adenocarcinoma participated in the trial. The results showed that the combination of Opdivo and chemotherapy significantly improved overall survival (OS). Median survival was 13.8 months in the Opdivo group and 11.6 months in the chemotherapy group.
In patients whose tumors expressed PD-L1 (CPS>5), the Opdivo combination was more effective, with a median OS of 14.4 months compared with 11.1 months for chemotherapy controls. The Opdivo combination reduced the risk of death by 29% (HR=0.71, 98.4% CI, 0.59-0.86, P <0.0001).
CheckMate-649 survival data (image: BMS website)
"For the first time in more than a decade, a first-line therapy approved today provides a survival benefit in patients with advanced or metastatic gastric cancer." "FDA is committed to bringing more safe and effective treatment options like Opdivo to patients with advanced cancer," said Dr. Richard Pazdur, director of the FDA's Center of Excellence on Oncology.