First Immunotherapy for Initial Treatment of Gastric Cancer Approved

The FDA approved nivolumab (Opdivo) in combination with certain types of chemotherapy for the initial treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer (GEJ), and esophageal adenocarcinoma.

The PD-1 inhibitor is the first immunotherapy agent to receive approval in the United States for patients with gastric cancer, which has about 28,000 new diagnoses annually. Overall survival is generally poor; the rate of cure with resection is very low and the survival rate for all stages is 32%. The 5-year survival rate for advanced or metastatic gastric cancer is 5%.

Data from the phase 3 CheckMate-649 trial showed that nivolumab in combination with leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CapeOX) resulted in a significant improvement in survival in treatment-naïve patients who had PD-L1–positive advanced gastric cancer, GEJ cancer, and esophageal adenocarcinoma vs chemotherapy alone.

At a minimum follow-up of 12 months, the median overall survival (OS) reported with nivolumab/chemotherapy was 14.4 months (95% CI, 13.1-16.2) compared with 11.1 months with chemotherapy alone (95% CI, 10-12.1) in patients who had a PD-L1 combined positive score (CPS) of 5 or greater (HR, 0.71; 98.4% CI, 0.59-0.86; P <.0001); this translated to a 29% reduction in the risk of death with the nivolumab combination.

Nivolumab plus chemotherapy also resulted in a 32% reduction in the risk of disease progression or death compared with chemotherapy alone (HR, 0.68; 95% CI, 0.56-0.81; P <.0001).

“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,” 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, said in a statement.

The trial enrolled a total of 1581 participants who were randomized 1:1 to receive either nivolumab at a dose of 360 mg in combination with CapeOX given every 3 weeks or nivolumab at a dose of 240 mg with FOLFOX given every 2 weeks (n = 789) versus CapeOX or FOLFOX alone (n = 792). Sixty percent of patients had a PD-L1 CPS of 5 or greater. The co-primary end points of the trial were OS and progression-free survival (PFS), while secondary end points comprised OS in all randomized patients and those with a PD-L1 CPS of 1 or greater.

The median OS in the combination arm was 14 months in those with a PD-L1 CPS of 1 or greater vs 11.3 months in the chemotherapy-alone arm (HR, 0.77; 99.3% CI, 0.64-0.92; P = .0001). Additionally, the median OS with the combination vs chemotherapy alone was 13.8 months and 11.6 months, respectively, among all patients who underwent randomization (HR, 0.80; 99.3% CI, 0.68-0.94; P = .0002).

Nivolumab, sold by Bristol-Myers Squibb, received Priority Review and Orphan Drug designations for this indication.

The most common adverse effects with nivolumab plus chemotherapy include peripheral neuropathy, nausea, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain, constipation and musculoskeletal pain. The immunotherapy agent can also cause immune-mediated effects like pneumonitis, colitis, and hepatitis, as well as endocrinopathies and nephritis.