Vemurafenib effective for some metastatic melanoma patients

Results from a phase II multi-center clinical trial involving 132 patients with previously treated BRAF V600-mutant metastatic melanoma, indicate that vemurafenib (PLX4032) - an oral BRAF inhibitor - offered a high rate of response in some patients. According to the researchers from the U.S. and Australia, including researchers at Moffitt Cancer Center in Tampa, Fla., over 50% of the study participants had positive, prolonged responses as well as a median survival of nearly 16 months. The study was published in the New England Journal of Medicine. Jeffrey S. Weber, M.D., Ph.D., director of the Donald A. Adam Comprehensive Melanoma Research Center at Moffitt, revealed that around 50% of melanomas contain the activating (V600) mutation threonine protein kinase B-RAF. However, for these patients treatment options are "limited." In both Phase I and Phase III trials, researchers have found the BRAF inhibitor vemurafenib to be effective. In this trial, designed by senior academic authors and representatives of the trial sponsor, Hoffman-La Roche, the team set out to determine the overall response rate in patients with stage IV melanoma who had previously received treatment. The trial, which included 132 patients, was open to individuals aged 18+ with histologically proven stage IV melanoma, progressive disease, who previously received systemic treatment. Weber explained: "Few patients with metastatic melanoma bearing the BRAF V600 mutation have a response to systemic chemotherapies. Additionally, most have a median survival of only six to 10 months. However, this study yielded an overall response rate of 56 percent and a median survival of nearly 16 months." According to the researchers, this response rate was higher than rates previous studies reported with other treatments for most of the participants, such as the monoclonal antibody impilimumab. They state that for participants in the vemurafenib Phase II trial, the response rate was "rapid," and that under 15% of study participants had disease progression at their first assessment. Weber concluded: "This trial showed that vemurafenib has clinically evident anti-tumor activity in metastatic melanoma, and that response rates are higher than those associated with previously used treatments." Although toxic effects were common, in the majority of cases they were not severe or life-threatening. The researchers note that, like the majority of targeted treatments designed to obstruct a driver oconogene, cancer cells can become resistant with continued dosing. Keiran S. Smalley, Ph.D., of the Moffitt Cancer Center, as well as other institutions are currently investigating the molecular mechanisms of vemurafenib in order to gain more insight into resistance.