Zelboraf (vemurafenib) is a selective inhibitor of the activated BRAFV600E gene, a gene found in 70% of malignant melanomas and a significant percentage of other cancers.
Zelboraf is speicfically indicated for the treatment of unresectable or metastatic melanoma with BRAFV600E mutation, as detected by an FDA-approved test.
Zelboraf is supplied as a tablet for oral administration. The recommended dose is 960 mg (four 240 mg tablets) twice daily. The first dose should be taken in the morning and the second dose should be taken in the evening approximately 12 hours later. Each dose can be taken with or without a meal. If a dose is missed, it can be taken up to four hours prior to the next dose to maintain the twice daily regimen. Both doses should not be taken at the same time.
The FDA approval of Zelboraf in treatment naïve subjects was based on an international, randomized, open-label trial in 675 subjects. The subjects received Zelboraf 960 mg by mouth twice daily or dacarbazine 1000 mg/m2 intravenously on Day 1 every three weeks. Treatment continued until disease progression, unacceptable toxicity, and/or consent withdrawal. The major efficacy outcome measures were overall survival (OS) and investigator-assessed progression-free survival (PFS). The overall response rate was 48.4% in the Zelboraf arm compared to 5.5% in the dacarbazine arm. There were two complete responses (0.9%) and 104 partial responses (47.4%) in the Zelboraf arm and all 12 responses were partial responses (5.5%) in the dacarbazine arm. The median progression free survival was 5.3 months in the Zelboraf arm versus 1.6 months in the dacarbazine arm. The FDA approval of Zelboraf in subjects who received prior systemic therapy was based on single-arm, multicenter, multinational trial in 132 subjects. The confirmed best overall response rate was 52%. There were three complete responses (2.3%) and 66 partial responses (50.0%). The median time to response was 1.4 months with 75% of responses occurring by month 1.6 of treatment. The median duration of response was 6.5 months.
Adverse events associated with the use of Zelboraf may include, but are not limited to, the following:
Vemurafenib is a low molecular weight, orally available, inhibitor of some mutated forms of BRAF serine-threonine kinase, including BRAFV600E. Vemurafenib also inhibits other kinases in vitro such as CRAF, ARAF, wild-type BRAF, SRMS, ACK1, MAP4K5 and FGR at similar concentrations. Some mutations in the BRAF gene including V600E result in constitutively activated BRAF proteins, which can cause cell proliferation in the absence of growth factors that would normally be required for proliferation.
Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O'Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA; BRIM-3 Study Group Improved survival with vemurafenib in melanoma with BRAF V600E mutation. The New England Journal of Medicine 2011 Jun 30;364(26):2507-16
For additional information regarding Zelboraf or BRAF+ melanoma, please visit the Zelboraf web page.