Penn study makes breakthrough in shrinking tumors of terminal melanoma patients

In a major advance against the deadliest type of skin cancer, a genetically targeted drug shrank tumors throughout the bodies of 80 percent of patients with terminal melanoma.

The study, led by the University of Pennsylvania and conducted at seven medical centers, is the first to successfully exploit a molecular abnormality found in about half of melanoma tumors, but not in healthy cells.

"This is the beginning of personalized medicine in melanoma," said senior author Paul Chapman, a melanoma researcher at Memorial Sloan-Kettering in New York City.

The drug - called PLX4032 until developers Plexxikon Inc. and Roche Pharmaceuticals give it a name - is the second recent breakthrough against a disease that had not had one in 20 years. In June, researchers reported that ipilimumab, an immune-stimulating drug being developed by Bristol-Myers Squibb and Medarex Inc., extended survival for patients whose melanoma had metastasized from the skin to internal organs.

The only two therapies currently approved by the Food and Drug Administration for metastatic melanoma do not work for most patients, and do not improve survival even in those who respond. Thus, a melanoma diagnosis is grim unless the malignancy is caught early enough to be cured by surgery.

And melanoma is becoming increasingly common. In the United States - where there were about 69,000 new diagnoses and 9,000 deaths last year - the percentage of people who develop melanoma has more than doubled in the last 30 years, according to the National Cancer Institute.

PLX4032 targets a mutation in a growth-promoting gene called BRAF. Research indicates that 40 percent to 60 percent of melanoma patients - and 8 percent of all cancers - have this BRAF gene mutation, according to the study, published Thursday in the New England Journal of Medicine.

Even so, focusing on BRAF was a gamble, as Keith Flaherty, the former University of Pennsylvania oncologist who led the study, was well aware. By the time the first PLX4032 patients were enrolled about two years ago, Flaherty had shown that Nexavar, an anti-BRAF drug approved to treat kidney cancer, did not work against melanoma, even when combined with standard chemotherapy.

Skeptics doubted that the BRAF gene was a good target for melanoma, a complex disease that can defy treatment by switching molecular signals and pathways.

Those doubts grew when the first group of patients did not respond to PLX4032, even at high doses.