The Food and Drug Administration (FDA) has approved Opdivo® (nivolumab; Bristol Myers Squibb), in combination with fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

The approval was based on data from the multicenter, randomized, open-label phase 3 CheckMate-649 trial (ClinicalTrials.gov: NCT02872116), which included 1581 adults with previously untreated advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. Patients were randomly assigned to receive nivolumab plus chemotherapy or chemotherapy alone; chemotherapy consisted of leucovorin, 5-fluorouracil and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CapeOX).

Results showed that treatment with nivolumab plus chemotherapy statistically significantly improved overall survival (OS) for all patients vs chemotherapy alone (hazard ratio [HR] 0.80; 95% CI, 0.71-0.90; P =.0002). Statistically significant improvements in OS (hazard ratio [HR] 0.71; 95% CI, 0.61-0.83; P <.0001) and progression-free survival (HR 0.68; 95% CI, 0.58-0.79; P <.0001) were also observed in nivolumab-treated patients with PD-L1 combined positive score (CPS) greater than or equal to 5.

In an exploratory analysis of all patients, 55% of patients in the nivolumab plus chemotherapy arm were alive at 1 year vs 48% of patients in the chemotherapy arm. Among patients with PD-L1 CPS less than 1, the median OS was 13.1 months (95% CI, 9.8-16.7) for the nivolumab plus chemotherapy arm vs 12.5 months (95% CI, 10.1-13.8) for the chemotherapy arm, with a stratified HR of 0.85 (95% CI, 0.63-1.15). Among patients with PD-L1 CPS less than 5, the median OS was 12.4 months (95% CI, 10.6-14.3) for the nivolumab plus chemotherapy arm vs 12.3 months (95% CI, 11.0-13.2) for the chemotherapy arm, with a stratified HR of 0.94 (95% CI, 0.78-1.14).


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As for safety, the most common adverse reactions (incidence of greater than or equal to 20%) for nivolumab in combination with chemotherapy included peripheral neuropathy, nausea, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain, constipation, and musculoskeletal pain.

“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.

References

  1. FDA approves first immunotherapy for initial treatment of gastric cancer. [press release]. Silver Spring, MD: US Food and Drug Administration; April 16, 2021. 
  2. 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. [press release]. Princeton, NJ: Bristol Myers Squibb; April 16, 2021.
  3. Opdivo [package insert]. Princeton, NJ: Bristol Myers Squibb; 2021.