November 11, 2010

New melanoma therapy shows promise in trial

Jeffrey A. Sosman Jeffrey Sosman (Vanderbilt)

New melanoma therapy shows promise in trial

A clinical trial of a new experimental therapy for metastatic melanoma being tested at Vanderbilt and several other medical centers has shown positive results, including tumor shrinkage in the majority of patients.

The results support previously reported positive data for the drug, known as PLX4032 (RG7204), in a much larger patient population where all responses were confirmed by an independent review committee.

Jeffrey Sosman, M.D.

Jeffrey Sosman, M.D.

Jeffrey Sosman, M.D., director of the Melanoma Program at Vanderbilt-Ingram Cancer Center (VICC), presented the data from the phase 2 clinical trial at the International Melanoma Research Congress of the Society for Melanoma Research in Sydney, Australia.

Melanoma is the most serious type of skin cancer and is growing at a rate of about five percent to six percent annually.

It is one of the deadliest cancers, with a historical five-year survival rate of less than 15 percent due, to the lack of effective treatments.

The new drug, which is being co-developed by Plexxikon and Roche, is a novel, oral, small molecule drug which targets melanoma and other cancers that harbor a mutation known as BRAF V600.

The trial is a single-arm study of previously treated metastatic melanoma patients who have the BRAF V600 mutation.

The multi-center study enrolled 132 patients and data showed a confirmed response rate of 52 percent, including three confirmed complete responses and 66 confirmed partial responses (tumor shrinkage of at least 30 percent).

“PLX4032 represents a true paradigm shift in the treatment of melanoma and a real breakthrough in melanoma research,” said Sosman, principal investigator. “For the first time, we have the possibility of offering a true personalized medicine targeted to melanoma patients who will benefit most from the treatment.”

Igor Puzanov, M.D., assistant professor of Medicine, is also participating in the trial.

VICC is now routinely testing all melanoma patients for the BRAF mutation as part of its newly launched Personalized Cancer Medicine Initiative.

The most common drug-related adverse events for PLX4032 were rash, photosensitivity, hair loss and joint pain. These were predominantly mild or moderate in severity.

Twenty-six percent of patients developed cutaneous squamous cell carcinoma, which was typically managed with limited surgery, which did not interrupt treatment.

In addition, 39 patients had stable disease. The median progression-free survival (PFS) was 6.2 months, compared to historical PFS of less than two months. The median duration of response was 6.8 months. Median overall survival has not yet been reached.