SATURDAY, Sept. 29 (HealthDay News) -- Researchers say they've discovered a two-drug combination that delays treatment resistance in patients with advanced melanoma.
By targeting different points in the same growth-factor pathway, the kinase inhibitor drugs dabrafenib and trametinib postponed the development of drug resistance in patients with BRAF-positive metastatic melanoma, the study authors said.
Melanoma is the most serious, and often deadly, form of skin cancer. In about half of patients with melanoma that has spread, tumor growth is caused by genetic mutations that keep the BRAF protein -- part of the MAPK cell growth pathway -- constantly activated. Drugs that inhibit BRAF activity can rapidly stop and reverse tumor growth in about 90 percent of patients. But the response is temporary in most cases, and tumor growth resumes in six or seven months, the researchers explained.
Previous research suggested that this drug resistance develops because the MAPK pathway gets turned back on through activation of MEK, another protein that is part off the MAPK pathway.
"We investigated this (drug) combination because of research we and others have conducted into the molecular underpinnings of resistance to BRAF inhibitor therapy," study lead author Dr. Keith Flaherty, of the Massachusetts General Hospital Cancer Center, said in a hospital news release.
The phase 1 and 2 study was sponsored by GlaxoSmithKline, which developed both drugs.
"We found that adding the MEK inhibitor trametinib to BRAF inhibitor dabrafenib clearly delays the emergence of resistance. In fact, the combination was at least twice as effective as BRAF inhibition alone," he said.