FDA approves dabrafenib and trametinib for advanced skin cancer

FDA has approved dabrafenib (Tafinlar, GlaxoSmithKline) and trametinib (Mekinist, GlaxoSmithKline) for patients with advanced (metastatic) or unresectable melanoma.

In addition, the Agency also approved Tafinlar and Mekinist with a  genetic test (THxID-BRAF, bioMérieux S.A) that will help determine if a patient’s melanoma cells have the V600E or V600K mutation in the BRAF gene.

Tafinlar is a BRAF inhibitor and is indicated as a single-agent oral treatment for unresectable melanoma or metastatic melanoma in adult patients whose tumors express the BRAF V600E gene mutation.

Tafinlar is not indicated for the treatment of patients with wild-type BRAF melanoma. Mekinist is an MEK inhibitor and is indicated as a single-agent oral treatment for unresectable or metastatic melanoma in adult patients with BRAF V600E or V600K mutations. Mekinist is not indicated for the treatment of patients who have received a prior BRAF inhibitor therapy.

According to the American Cancer Society in 2013 about 76,690 new melanomas will be diagnosed (about 45,060 in men and 31,630 in women). The rates of melanoma have been rising for at least 30 years. In addition, about 9,480 people are expected to die of melanoma (about 6,280 men and 3,200 women).

“The FDA approval of Tafinlar and Mekinist offers additional therapeutic options that will be available to the public, and also an opportunity for more aggressive treatments to target this form of cancer through 2 different mechanisms of action,” said Formulary Advisor Abimbola Farinde, PharmD, MS, clinical staff pharmacist at Clear Lake Regional Medical Center in Webster, Texas.

In March 2011, FDA approved ipilimumab (Yervoy, Bristol-Myers Squibb) to treat patients with late-stage (metastatic) melanoma. In August 2011, FDA approved vemurafenib (Zelboraf, Genentech) to treat patients with metastatic or unresectable melanoma, with cobas 4800 BRAF V600 Mutation Test (Roche Molecular Systems), a companion diagnostic to help determine if a patient’s melanoma cells have the BRAF V600E mutation.

Tafinlar was studied in 250 patients with BRAF V600E gene mutation-positive metastatic or unresectable melanoma. Patients were randomly assigned to receive Tafinlar or the chemotherapy drug dacarbazine. Patients who took Tafinlar had a delay in tumor growth that was 2.4 months later than those receiving dacarbazine.

The most serious side effects reported in patients receiving Tafinlar included an increased risk of skin cancer (cutaneous squamous cell carcinoma), fevers that may be complicated by hypotension, severe rigors, dehydration, kidney failure, and increased blood sugar levels requiring changes in diabetes medication or the need to start medicines to control diabetes.

Side effects most commonly reported in patients receiving Tafinlar included thickening of the skin, headache, fever, joint pain, non-cancerous skin tumors, hair loss, and hand-foot[m1]  syndrome.

Mekinist was studied in 322 patients with metastatic or unresectable melanoma with the BRAF V600E or V600K gene mutation. Patients were randomly assigned to receive either Mekinist or chemotherapy. Patients receiving Mekinist had a delay in tumor growth that was 3.3 months later than those on chemotherapy. Patients who previously used Tafinlar or other inhibitors of BRAF did not appear to benefit from Mekinist.

The most serious side effects reported in patients receiving Mekinist included heart failure, lung inflammation, skin infections, and loss of vision. Common side effects included rash, diarrhea, tissue swelling (peripheral edema), and skin breakouts that resemble acne.

Women of child-bearing years should be advised that Tafinlar and Mekinist carry the potential to cause fetal harm. Men and women should also be advised that Tafinlar and Mekinist carry the potential to cause infertility.