FDA drugs

Patients with advanced or inoperable melanoma have two new drugs that may delay tumor growth longer than existing chemotherapy. Here, a malignant "type A" mole. (Skin Cancer Foundation / April 23, 2008)

The Food and Drug Administration on Wednesday announced its approval of two new drugs and a diagnostic test that can be used to treat advanced or inoperable melanoma, the most dangerous form of skin disease.

Advanced melanoma has joined a wide range of cancers for which treatment is increasingly personalized, with genomic diagnostics and targeted drugs that promise greater effectiveness than old-fashioned chemotherapy.

The newly approved drugs, dabrafenib (to be marketed as Tafinlar) and trametinib (to be marketed as Mekinist), are to be used individually, not as a combination treatment, the FDA said. Tafinlar would be used in patients whose tumors express a gene mutation known as BRAF V600E. Mekinist could be used for those same patients, as well as for those who tumors express the BRAF V600K gene mutation.

A genetic test developed alongside those drugs, and also approved by the FDA on Wednesday, will help physicians identify patients who could benefit most from the BRAF-inhibitor drugs. The test is called the THxID BRAF test and is manufactured by BioMerieux of Grenoble, France. GlaxoSmithKline is the company marketing the two drugs, Tafinlar and Mekinist.

The two new drugs join ipilimumab (marketed as Yervoy) and vemurafinab (marketed as Zelboraf) -- both approved in 2011 by the FDA -- in treating melanoma that is advanced and/or inoperable. Yervoy is also a BRAF inhibitor, whereas Zelboraf stimulates the immune system to fight the cancer.

Though physicians and patients had high hopes that Yervoy and Zelboraf could be paired as a combination therapy, early trials of the two used together have suggested the combination is toxic to the liver.

Trials assessed by the FDA showed that advanced melanoma patients who got Tafinlar had a delay in cancer growth that was 2.4 months longer than patients who got a standard chemotherapy drug, dacarbazine. The most common side effects of Tafinlar were thickening of the skin, headache, fever, joint pain, non-cancerous skin tumors, hair loss and hand-foot syndrome. The most serious side effects were an increase in squamous cell carcinoma, fevers that were complicated by low blood pressure, dehydration, kidney failure and increased blood sugar levels that could require diabetes medication or an adjustment to an existing regimen of such medication.

Trial results considered by the FDA showed that subjects with the BRAF V600E or V600K gene mutation who got Mekinist had a delay in cancer growth that was 3.3 months longer than that seen in subjects who got standard chemotherapy. The most common side effects were rash, diarrhea, tissue swelling and acne-like breakouts, and the most serious side effects were heart failure, lung inflammation, skin infections and vision loss.

The findings suggested that patients who got Tafinlar or another BRAF inhibitor first did not benefit from Mekinist.