FDA approves ‘breakthrough’ melanoma drug

The Food and Drug Administration has granted accelerated approval to pembrolizumab (Keytruda, Merck) for treatment of advanced or unresectable melanoma in patients who have stopped responding to other drugs.

According to an FDA news release, Keytruda is the sixth new melanoma treatment approved since 2011 and the first that blocks a cellular pathway known as PD-1, which restricts the immune system from attacking melanoma cells. The drug is intended for use following treatment with ipilimumab. For patients whose tumors express the BRAF V600 gene mutation, Keytruda is intended for use after treatment with ipilimumab and a BRAF inhibitor.

The five prior FDA approvals for melanoma are ipilimumab, peginterferon alfa-2b, vemurafenib, dabrafenib and trametinib.

The FDA accelerated approval resulted from preliminary clinical evidence that the drug - to which the FDA also granted received priority-review and orphan-product status - may offer significant improvement over other therapies. Keytruda’s efficacy was established in a clinical trial involving 173 advanced-melanoma patients whose disease had progressed despite treatment. All were treated with Keytruda, either at the recommended dose of 2 mg/kg or at a higher dose of 10 mg/kg.

Among the patients who received the recommended dose, approximately 24 experienced tumor shrinkage that lasted up to nearly nine months and continued beyond that in most patients. A similar percentage of patients experienced tumor shrinkage at the higher dosage.

Keytruda’s safety was established in a trial involving 411 patients with advanced melanoma. The most common side effects were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia and diarrhea. Although Keytruda has the potential for severe immune-mediated side effects involving the lungs, colon, hormone-producing glands and liver, such effects occurred infrequently among the 411 study participants.

Next: What does it mean for patients?

The FDA approval was applauded by the Melanoma Research Alliance (MRA), which has contributed substantial funds to immunotherapy research.

“This is the latest in a string of major breakthroughs in melanoma treatment that will galvanize the field of melanoma research and cancer treatment,” MRA President and CEO Wendy Selig said in a news release. “Though we have much work left to do, we are committed to funding breakthrough research to speed the delivery of cures to all melanoma patients.”

Norman Levine, M.D., a dermatologist in Tucson, Arizona, tells Dermatology Times that Keytruda represents another novel treatment strategy aimed at halting the progression of advanced melanoma.

“The preliminary data is encouraging, but the real proof of the value of this medication will be whether survival will be enhanced,” he says. “At this stage, few if any dermatologists outside of those in academic medical centers will likely use this medication.”

Dermatologist Ronald Wheeland, M.D., who practices in Columbia, Missouri, agrees.

“I don’t know a single dermatologist who is treating patients with this stage of disease - rather, those patients are being cared for by oncologists at cancer centers almost routinely,” he tells Dermatology Times. “Of greater importance to dermatologists is being aware of this drug so they can provide more realistic information to patients under their direct care so they can receive the best possible care by oncologists.

“This diagnosis used to be a death sentence, so dermatologists must be made aware of the treatment possibilities and not paint such a negative picture about their patients’ futures,” Dr. Wheeland says.

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