• Yasser Heakal, Mark Kester, and Scott Savage.
• Lineberger Comprehensive Cancer Center and North Carolina Cancer Hospital, College of Medicine, University of North Carolina, Chapel Hill, NC, USA.
• Ann Pharmacother. 2011 Nov 1; 45 (11): 1399-405.

ObjectiveTo summarize the preclinical and clinical data on vemurafenib, approved by the Food and Drug Administration (FDA) on August 17, 2011, and discuss the drug's clinical advantages and limitations.Data SourcesAn English-language literature search of MEDLINE/PubMed (1966-August 2011), using the terms PLX4032, RG7204, RO5185426, vemurafenib, and metastatic melanoma, was conducted. In addition, information and data were obtained from meeting abstracts, clinical trial registries, and news releases from the FDA.Study Selection And Data ExtractionAll relevant published articles and abstracts on vemurafenib were included. Clinical trial registries and meeting abstracts were used to obtain information regarding ongoing trials. All peer-reviewed articles containing information regarding the clinical safety and efficacy of vemurafenib were evaluated for inclusion.Data SynthesisBefore the recent approval (March 2011) of ipilimumab, there was no first-line standard-of-care therapy, with proven overall survival benefit, for the treatment of malignant metastatic melanoma. Unlike ipilimumab, which acts through immune-modulation, vemurafenib is a novel, molecularly targeted therapeutic with preferential efficacy toward a specific mutated oncogenic BRAF-signaling mediator. In recently published results of a Phase 3 clinical trial comparing dacarbazine with vemurafenib, vemurafenib prolonged progression-free and overall survival, with confirmed objective response rate of 48% (95% CI 42 to 55) versus 5% (95% CI 3 to 9) for patients who received dacarbazine (p < 0.001).ConclusionsVemurafenib offers a novel, first-line, personalized therapy for patients who have mutated BRAF. Clinical trials of vemurafenib in combination with ipilimumab or other targeted or cytotoxic chemotherapeutic agents may provide more effective regimens with long-term clinical benefit.

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