SDEF: New Melanoma Treatments Show Improved Survival

During the past 30 years, only two drugs – dacarbazine and interleukin-2 – have been approved by the Food and Drug Administration for treating metastatic melanoma, and while these drugs help control the disease in a small percentage of patients, they do not appear to improve survival.

However, agents introduced within the last 2 years are reported to improve survival, Dr. Richard D. Carvajal of Memorial Sloan-Kettering Cancer Center, said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

The first is ipilimumab (also known as MDX-010), a monoclonal antibody that binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA4). Normally, CTLA4 functions as one of several negative feedback mechanisms within the immune system. Treatment with ipilimumab takes away this negative feedback mechanism and allows the immune system to recognize and combat melanoma, Dr. Carvajal said.

Dr. Richard D. Carvajal

In one study reported last year, ipilimumab improved overall survival in patients with previously treated metastatic melanoma (N. Engl. J. Med. 2010;363;711-23). Specifically, patients who received ipilimumab plus glycoprotein 100 (gp100) vaccine had an overall survival of 10 months, while those who received gp100 alone had a survival rate of 6.4 months. The median overall survival for patients taking ipilimumab alone was 10.1 months.

Even more striking, the 1-year overall survival rate for patients receiving ipilimumab alone or in combination with the vaccine was approximately 45%, significantly better than the 1-year overall survival rate of 25% achieved with the vaccine alone.

The second agent, PLX4032 (also known as RG7204 or RO5185426), works by inhibiting the mutated BRAF protein found in about half of all cases of metastatic melanoma. In January, the manufacturer, Plexxikon, announced that a phase III clinical study showed a significant survival benefit in people with previously untreated BRAF V600 mutation-positive metastatic melanoma.

Study participants who received PLX4032 lived longer (overall survival) and also lived longer without their disease getting worse (progression-free survival), compared with participants who received dacarbazine, the current standard of care.

"As these are the first two drugs ever demonstrated to improve survival in patients with advanced melanoma, these recent developments are extremely significant breakthroughs for the management of this disease," Dr. Carvajal said.

Dr. Carvajal disclosed that he has served as a consultant for Novartis. SDEF and this news organization are owned by Elsevier.