Melanoma mutations spark tailored therapies with impressive response rates

August 1, 2011

There is a great need for new melanoma treatments, and there has been some progress in the last five years that has come about as a result of greater molecular understanding of melanoma, according to the director and chairman of the department of dermatology, Skin Cancer Center, University Hospital Essen, Germany.

Key Points

Essen, Germany - There is a great need for new melanoma treatments, and there has been some progress in the last five years that has come about as a result of greater molecular understanding of melanoma, according to the director and chairman of the department of dermatology, Skin Cancer Center, University Hospital Essen, Germany.

The median age of onset of melanoma is 50, and in 20 percent of cases, the cancers will metastasize. One of the goals of research is to try to identify who will develop melanoma, who will have melanoma that will metastasize and who will respond to treatment.

Research to date

A key study published last summer showed that use of the immune suppressor ipilimumab (which is being investigated in other cancers and which targets CTLA-4) produced a survival benefit in the treatment of metastatic melanoma (Subudhi SK, Callahan MK, Wolchok JD. Oncology (Williston Park). 2010;24(14);1280-1288; Hodi SF, O'Day SJ, McDermott DF, et al. N Engl J Med. 2010;363(8):711-723).

The identification of BRAF in 2002 was a turning point, as it revealed that genetic research can hold the clues to tailoring medicine to the individual melanoma patient, says Dr. Schadendorf. Investigators found BRAF somatic misssense mutations in 66 percent of malignant melanomas (Pollock PM, Meltzer, PS. Nature. 2002;417(6892):906-907).

Together, NRAS and BRAF mutations are found in nearly two-thirds of melanomas, and their detection has produced an opportunity to find agents that are specific to these targets.

"We needed time to get the formulation right," says Dr. Schadendorf. "We wanted to ensure there was enough pharmacokinetic activity in the tumor and the blood."

Indeed, there are multiple entities that occur in melanomas that arise from both chronically sun-damaged skin and nonchronically sun-damaged skin. There are also specific entities that affect acral melanomas and mucosal melanomas.