FDA approves combo treatment for melanoma

The Food and Drug Administration has approved GlaxoSmithKline’s Mekinist (trametinib) for use in combination with Tafinlar (dabrafenib) as a possible treatment for patients suffering from inoperable melanoma and certain types of metastatic melanoma.

The combination of drugs was approved through the FDA’s Accelerated Approval program and given Priority Review status. The approval is dependent on the results of an ongoing trial (referred to as MEK115306 or COMBI-d), which is designed to determine the benefit of the drug combination among this patient population.

The combination of drugs is approved for metastatic melanoma with BRAF V600E or V600K mutations, which must be detected via testing. Use of Tafinlar is contraindicated for patients with wild-type BRAF melanoma. The combination acts to inhibit both BRAF and MEK, while lessening the side effects of only inhibiting MEK. The combination also can increase the efficacy of BRAF inhibitors, which alone lasts about six months.

“The main efficacy endpoint of investigator-assessed overall response rate was 76 percent for dabrafenib in combination with trametinib, and 54 percent for dabrafenib alone,” Kiran Patel, M.D., GSK’s vice president and medicine development leader for oncology, tells Dermatology Times. “This is an important finding because it suggests that two drugs can work better together. In terms of dermatologists’ routine monitoring of patients for cutaneous squamous cell carcinoma (including squamous cell carcinomas of the skin and keratoacanthomas), the trial’s primary safety endpoint, the incidence rate was 7 percent for dabrafenib in combination with trametinib and 19 percent for dabrafenib alone.”

The accelerated approval is positive news for those patients with some of the most difficult cases of melanoma, says dermatopathologist Ronald Wheeland, M.D., who practices in Tucson, Ariz.

 “Unresectable and metastatic melanoma represent the most serious and difficult to manage forms of melanoma,” says Dr. Wheeland, who was not involved in the studies. “For this reason, it is great news that the FDA has granted an accelerated approval for the combination treatment of these forms of melanoma using trametinib and dabrafenib based on the results of clinical trials. While additional follow-up and study are needed to evaluate the clinical benefit of this combination therapy, early evidence suggests that this combined treatment may provide successful management of appropriate melanoma patients.”