Treatment for metastatic melanoma shows promise in preliminary trials

The problem is that melanoma treatments to date have not worked as well as drugs for other cancers, such as leukemia. For patients with metastatic melanoma, there are currently only two approved drugs and they succeed in only 10 to 20 percent of patients.

Flaherty pursued another approach, based on laboratory evidence showing that mutations in a gene called BRAF allow tumor cells to grow unchecked. The BRAF mutation is present in about 8 percent of all cancers, including thyroid, ovarian, and colorectal cancer, but it is most common in melanoma.

Flaherty’s team tested a drug called PLX4032 designed to shut down that mutant gene in two trials conducted at Mass. General and five other cancer centers. The first phase, designed to see what the best dose might be, enrolled 55 patients, 49 of whom had metastatic melanoma. The second phase measured the drug's effectiveness in 32 other people who had metastatic melanoma and carried the BRAF mutation in their tumors.

In the first phase, tumors shrank in 11 of the 16 patients who had metastatic melanoma and the BRAF mutation. Tumors also shrank in three patients with thyroid cancer and the BRAF mutation.

In the second phase, 24 patients’ tumors shrank and two patients’ tumors disappeared. Among these 26 melanoma patients, tumors did not grow for an average of nine months.

Some of the tumors developed resistance to the drug, which is not uncommon
for targeted therapies. Because cancer can arise from more than just one genetic mutation, treatments may need to combine drugs, following the cocktail approach used so successfully with HIV, he said.

“We’ve beaten down the tumors to a degree and we’re pleased with that,” Flaherty said. “Patients with symptoms feel better, but we’d like to think we have it on the run. If we can nail down what the resistance mechanism is, we can go to therapy number two.”

The experimental drug did have some side effects. Some patients developed rashes and squamous-cell skin cancer, which were successfully treated, the article says.

“The prospects for patients with metastatic melanoma have never been brighter, but the need for further progress through laboratory research and well-conducted clinical trials is as great as – or greater than – ever," Keiran Smalley and Dr. Vernon Sondak of the Moffitt Cancer Center and Research Institute in Tampa wrote in their editorial.

A larger trial of the drug is under way at 14 cancer centers that have enrolled a total of 140 patients, Flaherty said.

The trials reported in the New England Journal were funded by Plexxikon, which developed the BRAF-inhibiting drug, and Roche Pharmaceuticals, which later partnered with Plexxikon. Flaherty said he has served as a consultant for Roche but is not one now.