WASHINGTON -- Two new drugs for metastatic or inoperable melanoma, dabrafenib (Tafinlar) and trametinib (Mekinist), were approved by the FDA on Wednesday.
The agency also approved a companion diagnostic test for both agents to detect certain mutations in the BRAF gene that render melanoma cells susceptible to the drugs.
Dabrafenib is an inhibitor of the BRAF gene when it carries the so-called V600E mutation. Trametinib inhibits a target known as MEK and is effective primarily against melanomas carrying either the V600E or V600K mutations.
Approximately half of patients with malignant melanoma are marked by BRAF mutations, the FDA said.
The agency noted that dabrafenib and trametinib were approved separately as stand-alone drugs, not as a combination, although therapy with both drugs together has been tested clinically and appeared to be better than dabrafenib alone.
The diagnostic product, called the THxID BRAF test, was evaluated in the same clinical trials supporting the two drugs' approvals. It was used to select patients for the trials.
Dabrafenib's approval was based primarily on a trial in 250 patients randomized to the drug or a standard chemotherapy agent, dacarbazine. The BRAF inhibitor prolonged progression-free survival by 2.4 months, the FDA said.
Trametinib's pivotal trial involved 322 patients with a chemotherapy regimen as the comparator. Progression-free survival was extended by 3.3 months with trametinib. However, patients previously treated with other BRAF inhibitors, including dabrafenib, did not benefit from trametinib, according to the FDA.
Both drugs had a variety of side effects. For dabrafenib, these included hyperkeratosis, headache, fever, arthralgia, alopecia, hand-foot syndrome, and noncancerous skin lesions. More seriously but less commonly, some patients experienced cutaneous squamous cell carcinomas, hypotensive fever, dehydration, rigors, kidney failure, and hyperglycemia that sometimes required initiation of anti-diabetic drugs.
Adverse effects seen with trametinib included heart failure, pulmonary inflammation, skin infections, and vision loss, as well as less serious effects such as rash, diarrhea, peripheral edema, and acne-like skin eruptions.
Both of the new agents are manufactured by GlaxoSmithKline. The BRAF mutation test is sold by bioMerieux.
John Gever
Senior Editor
John Gever, Senior Editor, has covered biomedicine and medical technology for 30 years. He holds a B.S. from the University of Michigan and an M.S. from Boston University. Now based in Pittsburgh, he is the daily assignment editor for MedPage Today as well as general factotum on the reporting side. Go Pirates/Penguins/Steelers!
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