OBJECTIVE: To summarize the clinical development of dabrafenib and to highlight 
the clinically relevant distinct characteristics of dabrafenib in contrast to 
vemurafenib.
DATA SOURCE: An English-language literature search of MEDLINE/PubMed (1966-June 
2013), using the keywords GSK2118436, dabrafenib, vemurafenib, selective BRAF 
inhibitor, and advanced melanoma, was conducted. Data were also obtained from 
package inserts, meeting abstracts, and clinical registries.
STUDY SELECTION AND DATA EXTRACTION: All relevant published articles on 
dabrafenib and vemurafenib were reviewed. Clinical trial registries and meeting 
abstracts were used for information about ongoing studies.
DATA SYNTHESIS: BRAF(V600E) mutation confers constitutive BRAK kinase activation 
in melanoma cells, promoting tumor growth. This discovery led to the development 
of BRAF kinase inhibitors like vemurafenib and dabrafenib. Dabrafenib has been 
approved to treat patients with BRAF(V600E)-positive unresectable or metastatic 
melanoma based on its clinical benefit demonstrated in a randomized phase III 
study. It has also been shown to be safe and effective in patients with BRAF 
mutant advanced melanoma involving the brain. Dabrafenib is well tolerated, with 
the most common adverse effects being hyperkeratosis, headache, pyrexia, and 
arthralgia. Currently, there is no evidence to suggest that one BRAF inhibitor 
is superior to the other. With similar efficacy, therapy selection will likely 
be influenced by differential tolerability and cost.
CONCLUSIONS: Dabrafenib joins vemurafenib to confirm the superior clinical 
outcome of the BRAF inhibitors when compared with dacarbazine in patients with 
BRAF(V600E)-positive advanced melanoma. Active research is ongoing to expand its 
utility into the adjuvant setting and to circumvent rapid emergence of drug 
resistance.