New Therapies for Melanoma

More than 68,000 individuals were diagnosed with melanoma in the United States in 2010, and 8,700 people will die as a result of the disease, according to estimates by the National Cancer Institute. However, the outlook for patients may be about to change. In March of this year, the Food and Drug Administration (FDA) approved the drug ipilimumab (Yervoy) for the treatment of advanced melanoma. The drug—developed by Bristol-Myers Squibb and Medarex—works by blocking a molecule called CTLA-4, which interferes with the ability of  T cells to fight off foreign invaders, including abnormal cancer cells. The FDA approval was based on results of a phase III clinical trial (Hodi et al. N Engl J Med 2010;363:711–23) showing that the drug increased median overall survival compared to gp-100, an investigational cancer vaccine which was used as an active control. Ipilimumab is the first drug the FDA has approved for advanced melanoma in more than a decade—and is the first of a series of potential new drugs in the pipeline. Biovex is currently testing its drug OncoVEX^GM-CSF in phase III trials in thousands of patients with advanced melanoma. This drug uses a modified version of the herpes virus to specifically produce granulocyte macrophage colony-stimulating factor (GM-CSF) inside tumor cells; GM-CSF then stimulates immune cells to mount an attack on the tumor. The MAGE-A3 vaccine developed by GlaxoSmithKline is also being tested in a phase III trial of advanced melanoma. In addition, numerous companies are developing targeted therapies against the BRAF protein; the gene encoding this protein is mutated in many cases of melanoma. In recent phase II trials, a BRAF inhibitor being developed by Roche (RG7204) extended progression-free survival of patients with advanced melanoma whose tumors had the BRAF mutation. GlaxoSmithKline has also started late-stage trials of 2 new BRAF inhibitors for advanced stage melanoma in patients with the BRAF mutation.