Zelboraf: targeted protein kinase inhibitor for melanoma

Zelboraf (vemurafenib) is now available for the treatment of BRAF V600 mutation-positive unresectable or metastatic melanoma.

Zelboraf joins Yervoy (ipilimumab) as another targeted treatment for melanoma
Zelboraf joins Yervoy (ipilimumab) as another targeted treatment for melanoma
PHARMACOLOGY

Vemurafenib is an oral serine-threonine kinase inhibitor of mutated BRAF.1 It has marked antitunour effects against melanoma cell lines with the BRAF V600E mutation but not wild-type BRAF.2
    
CLINICAL STUDIES

The BRIM-3 study recruited 675 patients with previously untreated metastatic melanoma expressing the BRAF V600E mutation. Patients were randomised to receive either oral vemurafenib (960mg twice daily) or intravenous dacarbazine (1g/m2 every 3 weeks). The co-primary endpoints were overall and progression-free survival (PFS); interim analysis was planned following 98 deaths and final analysis following 196 deaths.2

Overall survival in the interim analysis and PFS in the interim analysis associated vemurafenib with a relative risk reduction of 63% in the risk of death and of 74% in the risk of either death or disease progression compared with dacarbazine (p<0.001 for both comparisons). Following recommendations from the independent review of the interim analyses, patients were switched from dacarbazine to vemurafenib to complete treatment. Overall response rates were 48% for vemurafenib and 5% for dacarbazine.2

Adverse events seen most commonly amongst patients who received vemurafenib included cutaneous events, arthralgia and fatigue. Investigators noted squamous cell carcinoma and keratoacanthoma (or both) in 18% of patients who received vemurafenib; all lesions were treated with simple excision.2

References:
1.    Zelboraf Summary of Product Characteristics, February 2012.
2.    Chapman PB et al. N Engl J Med 2011; 364(26): 2507-16.
    
View Zelboraf drug record

Further information: Roche

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