FDA approves two melanoma drugs

May 30, 2013

The FDA approved two drugs and a companion diagnostic for the treatment of advanced metastatic melanoma Wednesday, the organization announced.

The Food and Drug Administration has approved two drugs and a companion diagnostic for the treatment of advanced metastatic melanoma.

Tafinlar (dabrafenib) is a BRAF inhibitor approved to treat melanoma tumors that express the BRAF V600E gene mutation. Mekinist (trametinib) is a MEK inhibitor that is approved to treat tumors that express either the BRAF V600E or V600K gene mutations. The drugs are approved as single agents, not as a combination treatment, according to the agency’s news release.

The companion genetic test, called THxID, is aimed at helping doctors determine which BRAF genetic mutation a patient’s melanoma cells carry. Its approval is based on evaluation of its use during the trials for both dabrafenib and trametinib, in which it was used to select patients.

Approximately half of melanomas carry a BRAF gene mutation, according to the FDA.

“Advancements in our understanding of the biological pathways of a disease have allowed for the development of Tafinlar and Mekinist, the third and fourth drugs the FDA has approved for treating metastatic melanoma in the past two years,” says Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

Zelboraf (vemurafenib, Genentech) and Yervoy (ipilimumab, Bristol-Myers Squibb) were approved for the treatment of metastatic melanoma in 2011, the agency noted.

The approval for dabrafenib comes after study results indicated that tumor growth was delayed 2.4 months longer in patients taking the drug compared with those receiving the chemotherapy drug dacarbazine. The trial randomly assigned 250 patients with BRAF V600E gene mutation-positive metastatic or unresectable melanoma to receive treatment with dabrafenib or dacarbazine.

Side effects reported by patients included hyperkeratosis, headache, fever, joint pain, noncancerous skin tumors, hair loss and hand-foot syndrome. Serious, but less common adverse events included an increased risk of cutaneous squamous cell carcinoma, fever due to hypotension, rigors, dehydration, kidney failure and hypoglycemia requiring changes to or the initiation of diabetic treatment.

The study for trametinib randomly assigned 322 patients with metastatic melanoma carrying the BRAF V600E or V600K gene mutations to receive either trametinib or chemotherapy. Results demonstrated that trametinib delayed tumor growth 3.3 months longer than chemotherapy. However, patients previously treated with other inhibitors of BRAF, including dabrafenib, did not show any benefit in this study, the FDA noted.

Common side effects reported were rash, diarrhea, peripheral edema, and acne-like breakouts. Serious side effects included skin infections, pulmonary inflammation, heart failure and vision loss.

Both drugs may carry a potential risk to unborn fetuses in women of child-bearing age, as well as potential infertility in both men and women.

GlaxoSmithKline markets dabrafenib and trametinib. The THxID BRAF Kit is marketed by bioMérieux of Grenoble, France.