Vemurafenib is the first molecularly targeted therapy to be licensed in the US 
and Europe for treatment of advanced melanoma. Its mechanism of action involves 
selective inhibition of the mutated BRAF V600E kinase that leads to reduced 
signalling through the aberrant mitogen-activated protein kinase (MAPK) pathway. 
Its efficacy is restricted to melanomas carrying the BRAF V600E mutation, which 
is seen in approximately 50% of all melanomas. In a randomized phase III trial, 
it was superior to dacarbazine in first-line treatment of advanced melanoma, 
with an overall response rate (ORR) of 48% (95% CI 42, 45), an estimated 6-month 
progression-free survival (PFS) of 5.3 versus 1.6 months (hazard ratio [HR] 
0.26; 95% CI 0.20, 0.33; p < 0.001) and a statistically superior 12-month 
overall survival (OS) rate of 55% versus 43% (HR 0.62 [95% CI 0.49, 0.77]). 
Vemurafenib is generally well tolerated, but its use can be associated with 
development of cutaneous neoplasms such as squamous cell carcinoma (SCC) and 
keratoacanthoma (KA). These lesions can be excised safely without the need for 
withholding the drug or reducing its dose. Mechanisms of resistance to 
vemurafenib do not involve development of secondary mutations in the BRAF kinase 
domain, but may be related to BRAF V600E over-amplification, bypassing 
mechanisms via upregulation and overexpression of other components in the MAPK 
signalling cascade or activation of alternative pathways with potential to 
enhance cell growth, proliferation and survival. Clinical trials to test the 
efficacy of vemurafenib in combination with immunomodulatory agents, such as 
ipilimumab, and MAPK kinase (MEK) inhibitors, such as GDC-0973, in the treatment 
of advanced melanoma are currently underway. Also under investigation is the use 
of vemurafenib in other solid tumours with BRAF mutations, such as papillary 
thyroid cancer.