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FDA Approves Nivolumab in Combination With Chemotherapy for Metastatic Gastric Cancer and Esophageal Adenocarcinoma


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On April 16, 2021, the U.S. Food and Drug Administration (FDA) approved nivolumab (Opdivo) in combination with fluoropyrimidine- and platinum-containing chemotherapy for advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

CheckMate 649

The efficacy of the combination was evaluated in CheckMate 649 (ClinicalTrials.gov identifier NCT02872116), a randomized, multicenter, open--label trial that enrolled 1,581 patients with previously untreated advanced or metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma. PD-L1 combined positive score (CPS) was determined centrally using the Agilent/Dako PD-L1 IHC 28-8 pharmDx test.

Patients received nivolumab in combination with chemotherapy (n = 789) or chemotherapy alone (n = 792); study treatment was administered as follows:

  • Nivolumab at 240 mg with mFOLFOX6 (fluorouracil, leucovorin and oxaliplatin) every 2 weeks, or mFOLFOX6 every 2 weeks
  • Nivolumab at 360 mg with CapeOX (capecitabine and oxaliplatin) every 3 weeks, or CapeOX every 3 weeks.

The main efficacy outcome measures in CheckMate 649, assessed in patients with PD-L1 CPS ≥ 5 (n = 955), were progression-free survival assessed by blinded independent central review and overall survival. The trial demonstrated a statistically significant improvement in both progression-free survival and overall survival for patients with PD-L1 CPS ≥ 5.

Median overall survival was 14.4 months (95% confidence interval [CI] = 13.1–16.2 months) in the nivolumab-plus-chemotherapy arm vs 11.1 months (95% CI = 10.0–12.1 months) in the chemotherapy-alone arm (hazard ratio [HR] = 0.71, 95% confidence interval [CI] = 0.61–0.83, P < .0001). Median progression-free survival was 7.7 months (95% CI = 7.0–9.2 months) in the nivolu-mab-plus-chemotherapy arm vs 6.0 months (95% CI = 5.6–6.9 months) in the chemotherapy-alone arm (HR = 0.68, 95% CI = 0.58–0.79, P < .0001).

As an additional efficacy outcome measure, a statistically significant improvement in overall survival was also demonstrated for all randomly assigned patients (n = 1,581) irrespective of CPS, with a median overall survival of 13.8 months (95% CI = 12.6–14.6 months) in the nivolu-mab-plus-chemotherapy arm vs 11.6 months (95% CI = 10.9–12.5 months) in the chemotherapy-alone arm (HR = 0.80, 95% CI = 0.71–0.90, P = .0002).

The most common adverse reactions (with an incidence ≥ 20%) observed in patients receiving nivolumab in combination with fluoropyrimidine-containing and platinum-containing chemotherapy were peripheral neuropathy, nausea, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain, constipation, and musculoskeletal pain.

The recommended dosages of nivolumab in this setting are:

  • 360 mg every 3 weeks in combination with fluoropyrimidine- and platinum-containing chemotherapy every 3 weeks
  • 240 mg every 2 weeks in combination with fluoropyrimidine- and platinum-containing chemotherapy every 2 weeks. 

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