On April 16, 2021, the FDA approved the PD-1 inhibitor nivolumab (Opdivo; 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 (GEJ) cancer, or esophageal adenocarcinoma. Nivolumab was the first immunotherapy approved by the FDA for first-line treatment of gastric cancer.
The FDA approval was based on results of the CheckMate-649 study, a randomized, multicenter, open-label clinical trial of 1581 patients with metastatic gastric cancer, GEJ cancer, or esophageal adenocarcinoma. The main efficacy outcome measures in the 955 patients with PD-L1 expression ≥5% were progression-free survival (PFS) and overall survival (OS).
In the patients with PD-L1 expression ≥5%, the median OS was 14.4 months (95% confidence interval [CI], 13.1-16.2) in the nivolumab plus chemotherapy arm versus 11.1 months (95% CI, 10.0-12.1) in the chemotherapy-alone arm (P <.0001). The median PFS was 7 months (95% CI, 7.0-9.2) in the nivolumab arm versus 6 months (95% CI, 5.6-6.9) in the chemotherapy-alone arm (P <.0001). In the full study population (N = 1581), regardless of PD-L1 status, the addition of nivolumab resulted in a significant OS benefit. The median OS was 13.8 months (95% CI, 12.6-14.6) with nivolumab plus chemotherapy versus 11.6 months (95% CI, 10.9-12.5) with chemotherapy alone (P = .0002).
The most common (≥20%) adverse reactions with nivolumab plus chemotherapy were peripheral neuropathy, nausea, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain, constipation, and musculoskeletal pain.
