Opdivo Treatment for Gastric and GEJ Cancers


by Dr. C.H. Weaver M.D. 8/2020

There is a real need to improve therapeutic options for patients with esophageal and stomach cancer. Responses to the current standard chemotherapy in patients are short lived, and less than 6% of patients with metastatic disease survive beyond five years.

Checkmate-649 is a Phase 3 clinical trial that was designed to evaluate and compare Opdivo (nivolumab) immunotherapy plus chemotherapy to chemotherapy alone in patients with previously untreated, non-HER2-positive, advanced or metastatic gastric cancer, GEJ cancer or esophageal adenocarcinoma in patients whose cancers express PD-L1 with a combined positive score (CPS) ≥ 5.

PD-1 Checkpoint Inhibitors

Opdivo is a type of immunotherapy called a Checkpoint inhibitor that helps to restore the body’s immune system in fighting cancer by releasing checkpoints that cancer uses to shut down the immune system. PD-1 and PD -L1 are proteins that inhibit certain types of immune responses, allowing cancer cells to evade an attack by the body’s immune cells. Checkpoint inhibitor drugs that block the PD-1 pathway enhance the ability of the immune system to fight cancer. By blocking the binding of the PD-L1 ligand these drugs restore an immune cells’ ability to recognize and fight the lung cancer cells.

The Combined Positive Score (CPS) helps doctors predict which patients will best respond to treatment with a checkpoint inhibitor. The CPS is simply the number of PD-L1 staining cancer cells detected in a biopsy sample divided by the total number of cancer cells, multiplied by 100. The specimen should be considered to have PD-L1 expression if CPS ≥ 1.

Patients enrolled in Checkmate-649 that received chemotherapy were treated with FOLFOX or CapeOX every two or three weeks, respectively. All patients continued treatment for two years or until disease progression, unacceptable toxicity or withdrawal of consent. Preliminary study results have been released and the combination of Opdivo and chemotherapy improved survival duration and delayed cancer recurrence compared to treatment with standard chemotherapy alone in individuals a combined positive score (CPS) ≥ 5. Full trial results are expected to be published shortly.