ASCO: Trametinib improves survival in metastatic melanoma

(HealthDay) -- For patients with metastatic melanoma with activating mutations in serine-threonine protein kinase B-RAF (BRAF), treatment with the oral selective MEK inhibitor trametinib is associated with improved progression-free and overall survival, compared with chemotherapy, according to a study published online June 4 in the New England Journal of Medicine to coincide with presentation at the annual meeting of the American Society of Clinical Oncology, held from June 1 to 5 in Chicago.

Keith T. Flaherty, M.D., from the Massachusetts General Hospital Cancer Center in Boston, and colleagues conducted a phase 3 open-label trial involving 322 patients with metastatic melanoma with V600E or V600K BRAF mutations. Participants were randomly allocated in a 2:1 ratio to receive trametinib once daily (2 mg orally) or chemotherapy every three weeks (intravenous dacarbazine or paclitaxel). Crossover to trametinib was permitted for patients in the chemotherapy group who had disease progression.

The researchers found that the median progression-free survival was significantly higher in the trametinib group (4.8 versus 1.5 months; hazard ratio [HR] for disease progression or death, 0.45). Despite crossover, the overall survival rate at six months was 81 percent in the trametinib group and 67 percent in the chemotherapy group (HR for death, 0.54). The most common toxic effects in the trametinib group were rash, diarrhea, and peripheral edema, and these were managed by dose interruption and dose reduction.

"Trametinib, a MEK inhibitor, improved progression-free and overall survival, as compared with chemotherapy, in patients who had melanoma with a V600E or V600K BRAF mutation," the authors write. "Further work will be needed to determine the optimal role for trametinib in the treatment of metastatic melanoma."

The study was funded by GlaxoSmithKline, which manufactures trametinib; several authors disclosed financial ties to pharmaceutical companies, including GlaxoSmithKline.

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