In an accelerated approval process, the Food and Drug Administration has approved the use of the monoclonal antibody pembrolizumab for treatment of certain solid tumors that have a common biomarker, a first for the agency.
Pembrolizumab ( Keytruda ) was approved to treat patients whose tumors are metastatic or unresectable, and which have the biomarker microsatellite instability-high (MSI-H), also known as mismatch repair deficient (dMMR). This biomarker is found in many kinds of solid tumors, especially in colorectal and other gastrointestinal cancers, as well as endometrial cancer, and may make tumors more susceptible to host immune system activity. “Approximately 5% of patients with metastatic colorectal cancer have MSI-H or dMMR tumors,” according to the FDA statement announcing the approval.
The approval represents a first in cancer drugs because it centers around the MSI-H biomarker, rather than the particular body part or organ system affected by the tumor. “We have now approved a drug based on a tumor’s biomarker without regard to the tumor’s original location,” Richard Pazdur, MD , director of the FDA’s Oncology Center of Excellence, said in the agency’s press release.
Patients who are eligible for pembrolizumab under this approval are those whose solid tumors have progressed despite earlier treatment and who lack other treatment options; pembrolizumab was also approved for colorectal cancer patients whose cancers have progressed after treatment with some chemotherapy drugs.
Pembrolizumab received priority review from the FDA and was approved on the basis of five uncontrolled single-arm clinical trials. There were a total of 149 patients enrolled in the trials, and 15 different cancer types were represented. Colorectal and other gastrointestinal cancers and endometrial cancers were the most common types in the studies. Of the 149 patients, 39.6% had a complete or partial response, and of these responders, 78% had a response lasting at least 6 months.
Fatigue is a common side effect of pembrolizumab; anorexia, peripheral edema, rash, pruritis, hyperlipidemia, and electrolyte disturbances are also common. Because of the drug’s mechanism of action, it can cause immune-mediated side effects, such as pneumonitis, hepatitis, nephritis, and endocrinopathies.
Pembrolizumab is given as an intravenous infusion, usually once every 3 weeks. It targets the programmed death-1/programmed death-ligand 1 (PD-1/PDL-1) pathway to boost the immune system’s ability to target and kill cancer cells.
“This is an important first for the cancer community,” said Dr. Pazdur, who is also acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. The clinical trials were sponsored by Merck & Co., which markets Keytruda.
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