FDA Approves First-Line Immune Therapy Opdivo in Combination with Chemotherapy for Advanced Gastric, GEJ, and Esophageal Adenocarcinoma

On the 17th, the U.S. FDA announced the 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. The press release noted that this is the first immunotherapy approved by the FDA for the first-line treatment of gastric cancer.

Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. In China, it is the second most prevalent cancer after lung cancer. The incidence and mortality rates of gastric cancer in China account for 44% and 50% of the global totals, respectively. Eighty percent of Chinese patients with gastric cancer are already at an advanced stage at the time of diagnosis. For the majority of patients with advanced gastric cancer, chemotherapy has remained the first-line treatment option over the past few decades. However, the efficacy of chemotherapy is limited, and the five-year survival rate for patients with advanced or metastatic gastric cancer is only 5%.

Opdivo, developed by Bristol-Myers Squibb Company, is a monoclonal antibody targeting PD-1. It enhances the anti-cancer immune response of T lymphocytes by inhibiting the signaling pathways mediated by the PD-1 immune checkpoint protein, thereby suppressing tumor growth. Since receiving its initial FDA approval in 2014, it has been approved in more than 65 countries and regions worldwide for the treatment of various types of cancer, including melanoma and non-small cell lung cancer.

This approval is supported by the randomized, open-label, Phase 3 CheckMate-649 clinical trial. A total of 1,581 patients with previously untreated advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, and esophageal adenocarcinoma were enrolled in the trial. The results demonstrated that the combination therapy of Opdivo and chemotherapy significantly improved overall survival (OS). The median overall survival was 13.8 months in the Opdivo combination therapy group, compared with 11.6 months in the chemotherapy group.

In patients with tumor PD-L1 expression (CPS > 5), Opdivo combination therapy demonstrated superior efficacy, with a median overall survival (OS) of 14.4 months compared to 11.1 months in the chemotherapy control group. Opdivo combination therapy reduced the risk of death by 29% (HR = 0.71; 98.4% CI, 0.59–0.86; p < 0.0001).

▲Survival Data from CheckMate-649 (Image source: BMS official website)

“For the first time in more than a decade, today’s approved first-line therapy provides a survival benefit (compared with standard of care) for patients with advanced or metastatic gastric cancer,” said Dr. Richard Pazdur, Director of the FDA’s Office of Hematology and Oncology Products. “The FDA remains committed to bringing more safe and effective treatment options, such as Opdivo, to patients with advanced cancer.”

In China, Opdivo (Opdivo) was approved by the National Medical Products Administration of China last March for the treatment of patients with advanced or recurrent gastric or gastroesophageal junction adenocarcinoma who have previously received two or more systemic therapy regimens. Last week, Bristol-Myers Squibb Company announced the primary results of the CheckMate-649 Chinese subgroup. The results showed that in the Chinese population, first-line treatment with Opdivo (nivolumab) combined with chemotherapy for unresectable advanced or metastatic gastric cancer and gastroesophageal junction cancer achieved clinically meaningful benefits in overall survival and progression-free survival (PFS) compared to chemotherapy alone. The analysis results of the Chinese subgroup were consistent with those of the global overall population.

Beyond Opdivo, at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium held earlier this year, zanidatamab, a HER2-targeted bispecific antibody co-developed by BeiGene and Zymeworks; bemarituzumab, an FGFR2b monoclonal antibody co-developed by Five Prime Therapeutics (recently acquired by Amgen) and Zai Lab; and combination therapies involving the blockbuster PD-1 inhibitor Keytruda all achieved positive results in clinical trials for first-line treatment of gastric cancer.

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