Platinum-based chemotherapy has been the standard treatment for patients with metastatic gastric adenocarcinoma for over ten years. According to a recent article in Healio, the median survival is about nine to eleven months.
Approximately ninety-five percent of stomach cancers are adenocarcinomas that begin in the lining of the stomach (mucosa) However, these numbers have improved thanks to encouraging results from the CheckMate 649 clinical trial treating gastric esophageal cancers.
Adding Nivolumab to Chemotherapy
Nivolumab is a drug that adheres to the PD-1 protein and aids the immune cells in their attack on cancer.
Two-year data from CheckMate 649 showed that adding nivolumab to chemotherapy brought about a durable response for new and untreated patients. The trial focused on patients who have advanced gastric cancer, esophageal adenocarcinoma, or cancer of the gastroesophageal junction where the stomach is connected to the esophagus. The patients were enrolled in the trial whether or not there was evidence of PD-L1 expression.
If PD-1 is bound to PD-L1, it creates the effect of helping T-cells to kill other cells including cancer cells.
A Transformation
Immunotherapy has transformed the treatment of various tumor types. Physicians treating HER2-negative gastric adenocarcinoma now have an opportunity to extend survival longer than twelve months.
This report emphasizes the benefit of nivolumab plus chemotherapy in sustained survival. In fact, extended follow-up data for nivolumab and chemotherapy combined affirms its use as first-line therapy.
However, a Phase 3 study results were disappointing for a nivolumab plus Opdivo treatment where the drugs did not demonstrate improved survival when compared with nivolumab and chemotherapy.
Researchers conducted two additional studies. The first study consisted of 1,581 patients treated with chemotherapy and the nivolumab antibody while a second group in the study received chemotherapy as a single agent.
Results of the first study found continued improvement in overall survival (OS) for patients with PD-L1 when adding nivolumab to chemotherapy.
The second analysis, a chemotherapy-free arm of CheckMate 649, involved 813 patients receiving either nivolumab and ipilimumab or chemotherapy as a single agent. It was tested on patients in advanced stages of gastric cancer.
This combination failed to make improvements in OS and showed an unsatisfactory response rate.
Looking Forward
A 24-month follow-up of the CheckMate trial showed continued OS benefits from nivolumab chemotherapy combination.
The minimal benefit from nivolumab-ipilimumab versus the positive benefit from the chemotherapy and nivolumab combination appears to confirm the low sensitivity of gastric adenocarcinoma. It, therefore, requires the addition of other therapies in order to control the disease.
