FDA Breaks New Ground with Expanded Keytruda Indication

WASHINGTON -- In an unprecedented move, the FDA today granted accelerated approval to the cancer drug pembrolizumab (Keytruda) for treatment of any unresectable or metastatic solid tumor associated with the genetic abnormality known as microsatellite instability.

It's the first time the agency approved a cancer treatment or indication that is not for a tumor arising from a specific tissue type, but rather is based on presence of a particular biomarker irrespective of tumor type.

The new pembrolizumab approval covers adult and pediatric patients with any type of tumor that exhibits microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR). The indication includes tumors that progressed following prior treatment and have no suitable alternative therapies, as well as colorectal cancer that progressed during or after treatment with chemotherapy.

"This is an important first for the cancer community," Richard Pazdur, MD, of the FDA Office of Hematology and Oncology Products, said in a statement. "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 and dMMR are types of genetic abnormalities that affect cells' internal mechanisms to repair DNA damage. Cancer exploits the defects to perpetuate the development of abnormal cells. MSI-H and dMMR occur most often in colorectal, endometrial, and gastrointestinal cancers (including about 5% of patients with metastatic colorectal cancer). Less commonly, the defects occur in breast, prostate, bladder, thyroid, and several other types of cancer.

Support for the new indication came from data on 149 patients with MSI-H/dMMR-associated tumors enrolled in five uncontrolled clinical studies of pembrolizumab. Treatment with the drug led to objective responses in 40% of the patients, and the responses persisted for 6 months or longer in 78% of cases.

Pembrolizumab disrupts the PD-1/PD-L1 immune checkpoint pathway that modulates the human immune system's natural anticancer activity. The accelerated approval adds to the drug's existing list of approved indications comprising metastatic melanoma, metastatic non-small cell lung cancer, recurrent/metastatic head and neck cancer, refractory classical Hodgkin lymphoma and urothelial carcinoma.

Accelerated approval is a status that provides access to therapies that address a significant unmet clinical need. The approval is granted on the basis of preliminary studies and remains contingent on completion of confirmatory studies.

Pembrolizumab is marketed by Merck & Co.

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