Experimental melanoma drug shows promise in early trials

In collaboration with the Press Association

Scientists have presented early clinical trial results for a new drug for melanoma - the most dangerous form of skin cancer. The findings were presented at the European cancer congress ECCO 15 - ESMO 34.

Researchers at Memorial Sloan-Kettering Cancer Centre in the US carried out a small-scale study involving a new compound, called PLX4032, that blocks the activity of a faulty protein in cancer cells.

Faults in this protein, called BRAF, are believed to be involved in around half of melanomas and five per cent of bowel cancers.Scientists recruited 31 melanoma patients, all of whom had the BRAF fault. Researchers found that, of the 22 patients who had been assessed so far, 20 had responded to the drug. Around two thirds of them showed at least 30 per cent tumour shrinkage for at least a month.

Co-lead researcher Dr Paul Chapman commented: "We are very excited about these results. Of the 22 patients we have been able to evaluate so far, 20 have had some objective tumour shrinkage. This is impressive as they all had metastatic disease and most of them had failed several prior therapies.

"A lot of these patients were pretty sick but many of them had a significant and rapid improvement in the way they function. We've had patients come off oxygen and we've got several patients who have been able to come off narcotic pain medication soon after starting treatment."

Dr Chapman explained that the experimental treatment attacks a faulty signal inside cells, whereas most chemotherapy drugs interfere with DNA replication.

"PLX4032 is different because it attacks the genetic programme that is causing the cells to divide uncontrollably, and we think the BRAF mutation is driving that programme," he revealed.

"The drug is blocking the genetics of the tumour, rather than trying to interfere with the proliferation of the cells and, as a result, there are fewer side-effects."

A further small-scale trial of PLX4032 involving 90 patients is expected to start later this year, followed by a larger phase III trial in North America, Europe and Australia.

Dr Chapman emphasised that it is too early to think of PLX4032 as a cure for advanced melanoma, but described the results as a "huge step forward".

Dr Kat Arney, Cancer Research UK's senior science information officer, commented: "Cancer Research UK and others have been investigating drugs that can block faulty BRAF, so it is interesting to see the results from a small-scale trial of such a drug.

"Melanoma is a very difficult cancer to treat and the results of this early-stage trial are promising, but larger trials need to be done before we know for sure how effective this treatment is."


P. Chapman et al, Early efficacy signal demonstrated in advanced melanoma in a phase I trial of the oncogenic BRAF-selective inhibitor PLX4032European Journal of Cancer Supplements Vol. 7, No 3, September 2009