A breakthrough clinical trial for people with advanced melanoma has established a new treatment protocol for the deadly skin cancer: the study showed a combination of two drugs targeting different parts of the melanoma worked better than either alone, to stop the growth of disease.
The results of the phase III clinical trial, involving 495 patients with BRAF-positive melanoma from 20 countries, presented by study-lead Professor Grant McArthur from Melbourne’s Peter MacCallum Cancer Centre at the European Society for Medical Oncology’s 2014 Congress in Madrid, Spain, overnight, and published today in the world’s pre-eminent medical publication, the New England Journal of Medicine, are an important step forward in understanding the mechanisms of targeted melanoma therapies.
Professor McArthur, Chair of the Melanoma and Skin Service and Head of the Cancer Therapeutics Program at Peter Mac, says the drugs, vemurafenib and cobimetinib, work together synergistically to attack the melanoma in two places.
‘We compared the single-use of vemurafenib — which blocks the cancer-causing activity of the mutated BRAF gene, responsible for around half of all melanomas — with a combination of vemurafenib and cobimetinib, which targets a different gene, called MEK, that is required for the activity of BRAF.
‘We found if we knocked out both BRAF and MEK simultaneously, we extended the average delay until the disease begins to grow again to almost ten months, compared to just over six months for those on vemurafenib alone.’
Professor McArthur says, while he’s seen many patients gain extra months and years of high-quality life while taking vemurafenib, usually the melanoma takes an alternative path, bypassing BRAF to activate the MEK gene, and kickstarting the growth of disease.
‘With these results we’ve found a way of circumventing an evasive tactic employed by the cancer to resist the effects of vemurafenib leading to an extension in progression-free survival that is incredibly important for these patients.’
Professor McArthur says the next phase of the research will involve returning to the laboratory to devise new approaches to overcoming resistance to this new, proven combination; understanding, predicting and blocking other ways in which melanoma may build resistance to these new drugs.