VEMURAFENIB APPROVED IN EUROPE

February 20, 2012 — The oral targeted agent vemurafenib (Zelboraf, Roche/Plexxikon) has been approved in Europe for use in the treatment of patients with advanced melanoma whose tumors have a BRAF mutation. The approval was widely expected after the product received a positive recommendation in December 2011 from the European Committee for Medical Products for Human Use.

About 50% of patients with melanoma have this BRAF mutation. A companion diagnostic test, the cobas 4800 BRAF V600 Mutation Test (Roche Molecular Systems), is already commercially available.

Vemurafenib is already available in the United States, where it was approved in August 2011. It is also approved in Brazil, Canada, Israel, New Zealand, and Switzerland. Approval applications are under review in Australia, India, Mexico, and other countries, according to a Plexxikon press release.

Significant Improvement in Survival

The approval was based on a pivotal phase 3 trial (known as BRIM-3) published last year (N Engl J Med. 2011;364:2507-2516), which showed a significant improvement in overall survival.

This trial was conducted in 675 patients with previously untreated unresectable or metastatic melanoma, who had all tested positive for the BRAF mutation. Patients were randomized to receive vemurafenib or standard treatment with dacarbazine.

The trial was halted early because of "compelling efficacy data," according to a Plexxikon statement. Vemurafenib reduced the risk for death by 63% (hazard ratio, 0.37; P < .0001).

A post hoc analysis showed that vemurafenib significantly improved median survival, compared with dacarbazine (13.2 vs 9.6 months). Historically, patients with metastatic melanoma have had a median survival of 6 to 10 months, the company noted.

The safety information about vemurafenib notes that the drug can cause a type of skin cancer — cutaneous squamous cell carcinoma; this adverse event has been previously reported by Medscape Medical News. The labeling for the product urges patients on the drug to check their skin and tell doctors about skin changes, including a new wart, a skin sore, a reddish bump that bleeds or does not heal, or a mole that changes size or color. In addition, patients on the drug should avoid the sun, and cover up when they are outside during the day.

Potential adverse events include severe allergic reactions, severe skin reactions, cardiac events such as QT prolongation (which can be potentially life-threatening), abnormal liver function tests, eye problems, and new melanoma lesions.

Common adverse effects include joint pain, rash, hair loss, tiredness, sunburn or sun sensitivity, nausea, itching, and warts.