An Immunotherapy Receives FDA Approval for Initial Gastric Cancer Treatment for the First Time

For advanced or metastatic gastric, gastroesophageal junction and esophageal adenocarcinoma, fluoropyrimidine- and platinum-containing chemotherapy combined with nivolumab (Opdivo) immunotherapy received approval on 16 April 2021 from the FDA (US Food and Drug Administration). It is the first FDA-approved first-line gastric cancer immunotherapy option.

This approval is for the first treatment in more than a decade to demonstrate a survival benefit in first-line treatment of patients with advanced or metastatic gastric cancer.

In Turkey each year, approximately 13 thousand new gastric cancers are diagnosed. Overall survival with currently available treatment is generally poor; the complete cure rate despite surgery is very low, and the overall 5-year survival rate in statistics including all stages is 32%.

Opdivo is a new-generation immunotherapy in the monoclonal antibody class that inhibits tumor growth by enhancing the function of T cells, a component of the immune system.

FDA Approval Based on the CHECKMATE-649 Study

The effectiveness of Opdivo in these cancers was evaluated in a randomized, multicenter, open-label trial involving 1,581 patients with previously untreated advanced or metastatic gastric, gastroesophageal junction and esophageal adenocarcinoma.

Patients received chemotherapy plus immunotherapy (789 patients) or chemotherapy alone (792 patients). Study drugs were administered as follows:

• Every 2 weeks, mFOLFOX6 (fluorouracil, leucovorin and oxaliplatin) plus 240 mg nivolumab (Opdivo), or mFOLFOX6 every 2 weeks.
• Every 3 weeks, CapeOX (capecitabine and oxaliplatin) plus 360 mg nivolumab, or CapeOX every 3 weeks.

Results

• The 789 patients receiving Opdivo with chemotherapy had longer median overall survival than the 792 receiving chemotherapy alone. Median overall survival was 13.8 months with Opdivo plus chemotherapy and 11.6 months with chemotherapy alone.
• This difference was greater in patients with PD-L1 combined positive score (CPS) ≥5: 14.4 months versus 11.1 months.
• Median progression-free survival (PFS) was 7.7 months in the nivolumab-plus-chemotherapy arm and 6 in the chemotherapy-alone arm (HR 0.68;95% CI: 0.58, 0.79; p <0.0001).

Side Effects

The most common side effects of Opdivo with chemotherapy include peripheral neuropathy (damage to nerves outside the brain and spinal cord), nausea, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain, constipation and musculoskeletal pain. Opdivo can cause serious conditions, including inflammation of healthy organs such as the lungs (pneumonia), colon (colitis), liver (hepatitis), endocrine glands (endocrinopathies) and kidneys (nephritis), known as immune-mediated side effects. Patients should tell their healthcare professionals before starting treatment if they have immune-system problems, lung or breathing problems, liver problems, have had an organ transplant, are pregnant or plan to become pregnant.

Recommended nivolumab doses are:

• 360 mg nivolumab every 3 weeks in combination with CapeOX chemotherapy every 3 weeks.
• 240 mg nivolumab every 2 weeks in combination with mFOLFOX6 chemotherapy every 2 weeks.