FDA Approves Nivolumab Plus Chemotherapy as 1L Therapy for Advanced or Metastatic Gastric Cancer

The FDA has approved nivolumab (Opdivo) in combination with certain chemotherapies for the initial treatment of advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, according to a press release by the FDA.¹

The approval of nivolumab marks the first FDA-approved first-line immunotherapy for gastric cancer. Every year, there are approximately 28,000 new diagnoses of gastric cancer, which has a generally poor survival rate. The current survival rate for all stages in 32%, with the 5-year survival rate of advanced or metastatic gastric cancer being 5%.

Approval of this immunotherapy and chemotherapy combination is based on findings from the randomized, multi-center, phase 3 CheckMate-649 study (NCT02872116), which showed that the addition of nivolumab improved overall survival (OS) and progression-free survival (PFS) compared with chemotherapy alone. In fact, patients lived on average 2.2 months longer than patients who received chemotherapy alone.^1,2

Additionally, the study showed that chemotherapy in combination with nivolumab reduced the risk of progression or death by 32%. The combination also not only more likely to produce a response, it also was associated with a longer duration of response.²

The trial had an estimated enrollment of 2032 participants with previously untreated advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. The FDA approval is based on data from 1581 patients. The study has the primary outcomes of overall survival (OS) and progression-free survival (PFS). Secondary outcomes include objective response rate (ORR) and time to symptom deterioration. 

During the study, patients were split into 5 arms. In arm 1, patients received a combination of nivolumab and ipilimumab for 4 doses, followed by nivolumab monotherapy. In arm 2, patients received a chemotherapy combination of oxaliplatin and capecitabine (XELOX). In arm 3, patients received the chemotherapy combination of oxaliplatin, leucovorin, and fluorouracil (FOLFOX). In arm 4, patients received a combination of nivolumab and XELOX. In arm 5, a combination of nivolumab and FOLFOX.

In order to be eligible to participate, patients must be 18 years old or older and have not received any neoadjuvant or adjuvant treatment for their disease within the last 6 months. Patients with the presence of tumor cells in the brain or spinal cord or with an active or suspected autoimmune disease are not eligible to participate.

In total, 789 patients received nivolumab in combination with chemotherapy, and 792 received chemotherapy alone. Of those patients, those who received the combination had a median survival of 13.8 months while those who received chemotherapy alone had a median survival of 13.8 months.

“Today’s approval is the first treatment in more than a decade to show a survival benefit for patients with advanced or metastatic gastric cancer who are being treated for the first time,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research in a press release. “The FDA is committed to bringing new safe and effective treatment options like Opdivo to patients with advanced cancer.”

Common adverse events (AE) observed with nivolumab in combination with chemotherapy include peripheral neuropathy, nausea, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain, constipation, and musculoskeletal pain. Grade 3-4 AE occurred in 5% or less of patients.²

Nivolumab is a monoclonal antibody that enhances T-cell function, inhibiting tumor growth. Nivolumab in combination with chemotherapy has shown clinical promise in other cancer types, including as a neoadjuvant treatment of resectable non-small cell lung cancer and unresectable advanced or metastatic esophageal squamous cell carcinoma.

_REFERENCE:

_{1.FDA approves first immunotherapy for initial treatment of gastric cancer. News release. FDA. April 16, 2021. Accessed April 16, 2021. https://bit.ly/32msDOs.}

_{2.Moehler M, Shitar K, Garrido M, et al. Nivolumab (nivo) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC)/esophageal adenocarcinoma (EAC): First results of the CheckMate 649 study. Ann Oncol. 2020; 31 (suppl_4): 1142-S1215. doi: 10.1016/annonc/annonc325}