FDA approves first cancer treatment for tumors flagged by MSI-H.

For the first time, the US FDA has granted accelerated approval for a new therapy to treat patients with cancers that have a specific genetic biomarker. Announced on May 23, the FDA said the precedent-setting therapy Keytruda (pembrolizumab) developed by Merck & Co., bases treatment not on the original location of the tumor, but on a common biomarker known as microsatellite instability-high (MSI-H).

According to the FDA, Keytruda is indicated for adult and pediatric patients that have unresectable or metastatic solid tumors identified by its MSI-H or mismatch repair deficient (dMMr) biomarker. Keytruda, said FDA, is for those with solid tumors that have not responded to prior therapies and have no “satisfactory alternative” treatment with other chemotherapy courses.

Regulators said Keytruda was approved using the Accelerated Approval pathway. The FDA’s approval rubric helps speed the approval of drugs for serious, life-threatening conditions where there is “unmet medical need” and a drug shows certain effects “reasonably likely” to predict a clinical benefit to patients.

Explaining how important this first-of-its-kind approval is, Richard Pazdur, Acting Director of the Office of Hematology and Oncology Products for FDA’s CDER and Director of the agency’s Oncology Center of Excellence said, “Until now, the FDA has approved cancer treatments based on where in the body the cancer started—for example, lung or breast cancers. We have now approved a drug based on a tumor’s biomarker without regard to the tumor’s original location.”

MSI-H or dMMR biomarkers have abnormalities that interrupt the repair of DNA inside the cell. The FDA noted that cancers containing these biomarkers are likely to be found in colorectal, endometrial and gastrointestinal cancers, as well as in (though less commonly) cancers found in the breast, prostate, bladder, thyroid gland and other organs in the body. The FDA estimates that 5% of patients with metastatic colorectal cancer have MSI-H or dMMR identified tumors.

Keytruda works by targeting and blocking the cellular pathway known as PD-1/PD-L1 (proteins found in immune cells and some cancer cells). Blocking this pathway, the FDA said, “may help the body’s immune system fight the cancer cells.” Prior to the approval, the FDA had approved Keytruda to treat patients with metastatic cancers: melanoma, non-small cell lung cancer, head and neck cancer, refractory classical Hodgkin lymphoma, and urothelial carcinoma.