A phase 1 clinical trial using a new formulation of an experimental drug that targets the BRAF cancer gene, has shown early promise in treating melanoma in patients with a mutated form of the gene and whose skin cancer has progressed to the metastatic stage.

A paper on the trial appears in the 26 August issue of the New England Journal of Medicine, NEJM.

Lead and corresponding author, Dr Keith Flaherty, director of Developmental Therapeutics at the Massachusetts General Hospital (MGH) Cancer Center in Boston, told the press that:

“Metastatic melanoma has a devastating prognosis and is one of the top causes of cancer death in young patients.”

In the US, the current prognosis for surviving metastatic melanoma, where the skin cancer has spread to other parts of the body, is about 9 months. About 9,000 Americans die of the disease every year.

Many melanomas have a mutation of BRAF that activates a protein called serine-threonine kinase (B-RAF or BRAF) that drives the growth of cancer cells. The mutation is called V600E. These mutations of BRAF also occur in other cancers.

In this phase 1 trial, Flaherty and colleagues from other research centers in the US and Australia, found that a new formulation of PLX4032 (an earlier formulation had not succeeded in a previous trial), inhibited the V600E mutation of BRAF and 26 of the 32 patients they treated with it (81 per cent) showed a partial or complete response that lasted at least 19 months.

The BRAF mutation that the new drug targets is active in more than half of all melanomas, and until this discovery patients and doctors had very few, reliable therapies. Flaherty said “these findings can really change the outlook for patients whose tumors are fueled by this mutation”.

If caught in the early stage, melanoma can often be removed surgically, but once the cancer has spread to other parts of the body, the chances of survival are vastly diminished.

There are FDA-approved drugs available, interleukin-2 and dacarbazine, however only 10 to 20 per cent of melanoma patients respond to them.

Researchers at the Sanger Institute in Britain discovered that the BRAF mutation drives cancer cell growth in 2002. Shortly after this Flaherty, who was at the University of Pennsylvania Abramson Cancer Center, began to investigate potential drugs that target the mutation as a way to interfere with tumor growth.

After experimenting with one drug that didn’t work, he teamed up with co-author Dr Paul Chapman from the Memorial Sloan-Kettering Cancer Center in New York, and they started working on PLX4032, an experimental drug developed by Plexxikon and licensed to Roche Pharmaceuticals, the two companies that funded this latest NEJM study.