Today, the U.S. Food and Drug Administration approved Keytruda (pembrolizumab) for intravenous injection for the first-line treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer. This marks the first immunotherapy approved for this patient population as a first-line treatment and which is administered to patients without also giving chemotherapy. 

MSI-H and dMMR tumors contain abnormalities that affect the proper repair of DNA inside the cell. The frequency of MSI-H varies across tumor types and stages, and approximately 5% of patients with metastatic colorectal cancer have MSI-H or dMMR tumors.

“Metastatic colorectal cancer is a serious and life-threatening disease with a poor prognosis. Available current therapy with chemotherapy combinations and other biologics are associated with substantial toxicity,” said Richard Pazdur, M.D., 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. “Having a non-chemotherapy option available for selected patients is a noteworthy paradigm shift in treatment.”

Keytruda works by targeting the cellular pathway of proteins found on the body’s immune cells and some cancer cells, known as PD-1/PD-L1. By blocking this pathway, Keytruda may help the body’s immune system fight the cancer cells and provide a benefit in patients with MSI-H or dMMR metastatic colorectal cancer. The FDA previously approved Keytruda to treat other types of cancer.

The FDA’s approval for this indication was based on the results of one multicenter, international, open-label, active-controlled, randomized trial that compared Keytruda with chemotherapy treatment in 307 patients with MSI-H or dMMR metastatic colorectal cancer. The study demonstrated a statistically significant improvement in progression-free survival (PFS) as assessed by blinded independent review. Median PFS was 16.5 months in the Keytruda group and 8.2 months in the standard of care group. Longer-term analysis is needed to assess for an effect on survival.