Metastatic melanoma is a disease with a poor prognosis and for which only two chemotherapeutic drugs, the alkylating agent dacarbazine (DTIC-Dome) and the new monoclonal antibody ipilimumab (Yervoy), have been approved for treatment. The effectiveness of these agents is limited, however, and response rates have been disappointing. Now a new BRAF kinase inhibitor, vemurafenib, looks promising. In a phase 2 trial it had a confirmed response rate of 53%, and a six-month analysis of a randomized phase 3 trial comparing vemurafenib with dacarbazine showed vemurafenib to be so effective that patients in the dacarbazine group were allowed to cross over to receive vemurafenib.

Figure. Kerri Adams, at her home near Oklahoma City in 2009, took part in a clinical trial of vemurafenib to treat her advanced melanoma. A few weeks after taking her first dose, she began to recover. Photo by Angel Franco /

All 675 patients in the study had unresectable, previously untreated stage IIIC or stage IV melanoma that tested positive for the BRAF V600E mutation, the BRAF mutation most commonly implicated in cutaneous melanomas. The primary end points were the rates of overall survival and progression-free survival. At six months, overall survival was 84% in the vemurafenib group and 64% in the dacarbazine group; the estimated median progression-free survival was 5.3 months in the vemurafenib group and 1.6 months in the dacarbazine group. The researchers concluded that their findings "provide a solid foundation for the development of future combination therapies."-David Carter

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