FDA Approves Nivolumab in Combination with Chemotherapy for Advanced, Metastatic Gastric Cancer

Officials with the FDA have approved nivolumab (Opdivo, Bristol Myers Squibb) in combination with chemotherapy for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, regardless of programmed death-ligand 1 (PD-L1).

According to a press release, nivolumab is the first and only immunotherapy in combination with chemotherapy to deliver superior overall survival (OS) compared to chemotherapy alone in this patient population.

Gastric cancer is estimated to impact approximately 26,560 people in the United States in 2021 alone, and approximately 90% to 95% of all gastric cancers are adenocarcinomas. Similarly, esophageal cancer is a type of gastrointestinal cancer with an expected 19,260 new cases diagnosed in 2021. Gastroesophageal junction cancers are on the rise and are typically treated similarly to esophageal cancers.

The FDA approval is based on the phase 3 CheckMate-649 trial, which evaluated nivolumab in combination with fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CapeOX).

The combination demonstrated superior OS, both in all randomized patients and in patients with a PD-L1 combined positive score of 5 or greater. In an exploratory analysis of all patients, 55% of those who received nivolumab were alive at 1 year compared to 48% of patients on chemotherapy alone. The combination treatment also significantly reduced the risk of disease progression or death compared to chemotherapy alone.

“In CheckMate-649, Opdivo plus chemotherapy combination significantly improved survival for patients with metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, reducing the risk of death by 20%,” said principal investigator Yelena Y. Janjigian, MD, in the press release. “Additionally, 55% of patients were still alive at 1 year. These findings are important, reinforcing the potential of this Opdivo-based combination as a standard of care for this population of patients in high need of treatment options that may extend their lives.”

Nivolumab is associated with several warnings and precautions, including severe and fatal immune-mediated adverse events (AEs), such as pneumonitis, colitis, hepatitis, and hepatoxicity; endocrinopathies; nephritis and renal dysfunction; dermatologic AEs; and complications of allogeneic hematopoietic stem cell transplantation. Researchers have also noted increased mortality in patients with multiple myeloma when nivolumab is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.

“We are focused on bringing transformative medicines to patients in need, and historically, there has been little progress for patients diagnosed with these metastatic gastroesophageal adenocarcinomas,” said Adam Lenkowsky, general manager and head of US Oncology, Immunology, and Cardiovascular at Bristol Myers Squibb, in a press release. “As demonstrated in the CheckMate-649 trial, Opdivo is the first and only immunotherapy combined with chemotherapy to deliver superior overall survival versus chemotherapy alone in first-line metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. Today’s approval may offer these patients hope for the chance at a longer life.”

REFERENCE

US Food and Drug Administration Approves Opdivo (nivolumab) in Combination with Chemotherapy for Patients with Advanced or Metastatic Gastric Cancer, Gastroesophageal Junction Cancer, and Esophageal Adenocarcinoma [news release]. Bristol Myers Squibb; April 16, 2021. https://news.bms.com/news/details/2021/U.S.-Food-and-Drug-Administration-Approves-Opdivo-nivolumab-in-Combination-with-Chemotherapy-for-Patients-with-Advanced-or-Metastatic-Gastric-Cancer-Gastroesophageal-Junction-Cancer-and-Esophageal-Adenocarcinoma/default.aspx. Accessed April 16, 2021.