The European Medicines Agency (EMA) has approved the MEK-inhibitor trametinib (Mekinist, GlaxoSmithKline) for the treatment of melanoma, following on from the positive opinion the product received in April 2014.
Specifically, trametinib is now approved for use as a single agent in adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation. Presence of this mutation must be confirmed with a validated test before therapy begins.
Trametinib is already approved for this same indication for use as a single agent in BRAF-mutated metastatic melanoma in the US.
Trametinib is also approved in the US for use in combination with dabrafenib (Tafinlar, GlaxoSmithKline), which has a slightly different mechanism of action (BRAF inhibition). The 2-drug combination was granted an accelerated approval by the Food and Drug Administration in January 2014 based on data on response rate and median duration of response in a phase 1/2 study.
However, these same data were recently rejected by the EMA Committee for Medicinal Products for Human Use (CHMP), who wanted to see more mature data.
First Drug in Its Class
Trametinib is the first drug in its class. It inhibits MEK, a protein present in the MAPK pathway, which regulates the normal growth and death of cells and plays a role in metastatic melanoma development. Some mutations in the BRAF gene can cause the MEK protein to stimulate cancer cell growth and survival, and so inhibiting MEK can potentially slow tumor growth in BRAF-mutant metastatic melanoma, according to the manufacturer.
The European approval for use of trametinib as a single agent is based on data from the randomized, open-label phase 3 METRIC study of 322 patients with BRAF-mutant melanoma (types V600E and V600K). These patients had either received no prior therapy or 1 prior chemotherapy treatment in the metastatic setting.
Trametinib showed a significant improvement in progression-free survival (PFS) compared with chemotherapy (hazard ratio, 0.45; P < .0001), with a median PFS of 4.8 months compared with 1.5 months for chemotherapy.
The most common adverse reactions (≥ 20%) for trametinib include rash, diarrhea, fatigue, peripheral edema, nausea, and dermatitis acneiform, the company notes.
In addition, special warnings and precautions for use of trametinib include cardiac disorders, hypertension, interstitial lung disease/pneumonitis, hemorrhage, rhabdomyolysis, visual impairment, rash, and hepatic events.
Medscape Medical News © 2014 WebMD, LLC
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Cite this: Trametinib (Mekinist) Now Approved in EU for Melanoma - Medscape - Jul 04, 2014.