May 18, 2012
Australian researchers reported promising results with a new drug that shrinks brain tumors in melanoma patients. Their findings are published in The Lancet medical journal today.
Medical researchers at Melanoma Institute Australia, Sydney's Westmead Hospital and Westmead Millenium Institute, and The University of Sydney say a new drug they have been testing to treat deadly melanoma in the body also shows, for the first time, an ability to shrink secondary tumours (metastases) in the brains of patients with advanced forms of the disease.
They say the new drug can add months to the lives of patients whose melanoma has spread to the brain. Most patients with brain metastases die within four months. The trial’s results, however, showed brain tumors in nine of the 10 patients shrank within the first six weeks. All 10 patients survived beyond five months, two patients survived beyond 12 months. One patient was alive at 19 months.
The drug called Dabrafenib works by targeting a gene mutation found in melanoma cancer, called the BRAF mutation, which is present in 50 per cent of human melanomas. The drug works by binding to the activated mutant form of the BRAF protein in the melanoma cell, causing the cell to stop proliferating. In many cases it shrinks and disappears.
The study focused on the most common BRAF gene mutation (V600E) and a particular type of the BRAF mutation (V600K) that is common in Australians where cumulative UV exposure from the sun is higher than in other parts of the world.
The lead author of the study, Dr Georgina Long, from Melanoma Institute Australia, Westmead Hospital and The University of Sydney, said, "This is the first evidence that we have a therapy that helps prolong survival in patients with multiple melanoma brain metastases. The findings are among the most important in the history of drug treatment for melanoma.
"Currently there is no effective systemic treatment for melanoma brain metastases, and patients whose cancer has spread to the brain are frequently excluded from promising clinical trials. Until now, there has not been a single drug that has shrunk brain metastases in more than ten out of 100 patients with metastatic melanoma. This drug had a 90 per cent success rate in reducing the size of brain metastases.
“Brain metastases in melanoma are a major unsolved problem. Until now, melanoma has been notoriously resistant to drug therapy in general, and responses in highly lethal brain metastases are particularly uncommon. Providing these early data are supported in larger cohorts of patients, and durable responses are confirmed, this activity in the brain may assist in addressing a large unmet need in patients with metastatic melanoma worldwide. Historically, researchers have been reluctant to concentrate on brain metastases because the survival period is so short,” Dr Long said.
But Dr Long and Westmead Hospital specialist Professor Rick Kefford AM, who also leads cancer research at the Westmead Millennium Institute for Medical Research and Melanoma Institute Australia, lobbied hard to extend the trial to focus directly on people with brain metastasis and the BRAF variation seen more commonly in Australia. They can take special credit for this trial’s success.
WMI senior researcher Dr Helen Rizos is leading a team working on the next steps for these drugs, which stop working after a time. Her team is defining mechanisms used by melanoma tumours to survive in the presence of these drugs.”
With this information we can design treatment strategies that can be used, often in combination with the initial drugs, to overcome resistance.”