New Melanoma Drug Creates Excitement

A new drug used to treat metastatic melanoma patients who have the genetic mutation known as BRAF^V600E demonstrated significant tumor shrinkage in the majority of patients during a clinical trial.

Data from the Phase 1 trial of drug PLX4032, developed by Plexxikon Inc. and Roche Pharmaceuticals, showed that nearly all patients with the mutation who were treated with the drug showed some response and 81 percent of patients had tumor shrinkage of at least 30 percent. The data were published in the New England Journal of Medicine.

Igor Puzanov, M.D.

Igor Puzanov, M.D., assistant professor of Medicine, and Jeffrey Sosman, M.D., professor of Medicine, Vanderbilt-Ingram Cancer Center (VICC), are among the Principal Investigators on the study. Keith Flaherty, M.D., Massachusetts General Hospital Cancer Center of Harvard University, is lead author.

Melanoma, a form of skin cancer, is curable when caught in its early stages but it can be lethal when it metastasizes to other areas of the body. Less than 10 percent of patients with metastatic melanoma are still alive five years after diagnosis, according to the National Cancer Institute.

“In the more than 20 years that I have been taking care of melanoma patients, I have not seen this kind of patient response to a therapy,” said Sosman, leader of the VICC Melanoma Program. “We finally have a way to identify patients with a specific genetic mutation who are most likely to benefit from a treatment, and a drug that targets that mutation. This is the promise of personalized medicine and Vanderbilt’s patients are benefiting from this approach to cancer treatment.”

In the melanoma extension cohort of the clinical trial, in which 32 metastatic melanoma patients with the BRAF mutation were enrolled, there were two complete responses with no evidence of disease, and 24 partial responses with tumor shrinkage of at least 30 percent. The estimated progression-free survival (PFS) among these patients was at least seven months as of January 31, 2010, compared less than two months in most clinical trials.

Jeffrey Sosman, M.D.

”This is a paradigm changing trial in melanoma treatment and a real breakthrough in melanoma research,” said Puzanov, associate director of the Phase 1 Drug Development Program at Vanderbilt-Ingram. “Our team is now involved in the next wave of trials, trying to improve these results further, hopefully leading to longer survival for patients.”

The PLX4032 drug, which is administered as a pill, is currently in parallel and ongoing Phase 2 and Phase 3 trials. The drug is a small molecule that is selective for a key oncogenic driver in melanoma and other cancers. Sosman is leading the Phase 2 trial.

While the majority of patients showed tumor shrinkage while taking the drug, the tumors eventually progressed in some cases. Investigators are now trying to determine other genetic pathways that are important in the progression of melanoma as they search for additional targeted therapies.

Drug-related adverse events during the trial included rash, joint pain, nausea, photosensitivity and fatigue. Some patients developed cutaneous squamous cell carcinoma in sun-exposed areas of the skin that was treated with surgery while treatment with PLX4032 was continued.

Learn More

See VIDEO interview with ABC News: Dr. Jeff Sosman explains how drug targets mutation.

Watch more about personalized cancer medicine in Your Genome and the Future of Medicine.

Learn more about the genome-driven therapy at Vanderbilt-Ingram Cancer Center.

Get information about our melanoma team and services, plus other resources.

Visit profiles for Drs. Puzanov and Sosman.