FDA Chalks Up a First by Approving Keytruda for Cancers with Specific Genetic Features

FDA Chalks Up a First by Approving Keytruda for Cancers with Specific Genetic Features

In a first, the U.S. Food and Drug Administration has approved a treatment for cancer patients with specific genetic features in their tumors rather than a specific tumor type.

The approval, based on clinical trial results of Merck‘s Keytruda (pembrolizumab), opens the way for Keytruda to be used against a number of cancers. The approval came under the FDA’s Accelerated Approval program, under which it can grant an approval early when a therapy meets an unmet need for a serious condition.

Keytruda can now be prescribed for adults and children with unresectable solid tumors who have the genetic biomarkers, known as microsatellite instability-high (MSI-H) and DNA mismatch repair (dMMR). Unresectable cancers are those that can’t be removed by surgery. Keytruda will be available only to patients whose cancer progressed after previous therapy and who have no treatment alternatives, however.

“This is an important first for the cancer community,” Dr. Richard Pazdur of the FDA said in a press release. “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.”

The genetic abnormalities in tumors with MSI-H and dMMR impair cells’ ability to repair DNA. This leads to an accumulation of the mutations in tumor cells. The mutations can generate structurally different proteins that the immune system identifies as malignant.

Keytruda is called an immune checkpoint inhibitor because it inhibits a protein in immune cells that prevents them from recognizing cancer cells. By doing this, it promotes the destruction of cancer cells.

MSI-H and dMMR are most commonly found in colorectal, endometrial, and gastrointestinal cancers, but can also be found in cancers of the pancreas, breast, bladder, thyroid, prostate, and others.

The FDA based its approval on five clinic trials involving 149 patients with 15 MSI-H or dMMR cancers, most of them colorectal, endometrial, and gastrointestinal. Participants received Keytruda in one of two dosing regimens: 200 mg every three weeks or 10 mg/km every two weeks.

Most participants received Keytruda for 24 months. Treatment was cut short when a patient was unable to tolerate it or their disease progressed. The five trials were uncontrolled, multi-cohort, multi-center, single-arm studies.

The primary measures of Keytruda’s effectiveness were patients’ objective response rate and the length of their response. An objective response is either a complete or partial response to a therapy.

Forty percent of the patients had an objective response to Keytruda. Eleven were complete responses and 48 partial responses. Seventy-eight percent of the complete and partial responses lasted at least six months.

Continued FDA approval of Keytruda’s use against cancers with the genetic abnormalities is likely to depend on clinical trials that confirm its benefits in those cancers.

Most patients in the trials were identified as having MSI-H or dMMR tumors before the start of the studies. Researchers used a genetic test after treatment to identify 14 others with the mutations.

The most common side effects of Keytruda in the trials were fatigue, itchy skin, diarrhea, loss of appetite, rash, fever, cough, breathlessness, muscoskeletal pain, nausea, and constipation.

Keytruda’s prescribing instructions include a caution that the drug’s safety and effectiveness have yet to be established in children with MSI-H central nervous system cancers.