Dabrafenib for the treatment of melanoma

Abstract

Introduction: Advanced melanoma carries a poor prognosis. Until 2011, the only available US FDA-approved therapies were intravenous dacarbzine and IL-2, neither of which was effective in the majority of patients treated. Ongoing molecular characterization of melanoma has revealed the presence of BRAF mutations in 50% of cases. Targeted therapy against mutant BRAF has emerged as a revolutionary and practice-changing approach in the management of advanced melanoma.

Areas covered: Dabrafenib is a selective, ATP-competitive inhibitor of the mutant BRAF kinase and was FDA approved in 2013 as monotherapy for treatment of BRAF V600E-mutated advanced melanoma. Additionally, it has demonstrated efficacy in treatment of melanoma brain metastases and is FDA approved in combination with the MEK inhibitor trametinib for melanomas with a BRAF V600E or V600K mutation. Through a comprehensive literature review, we summarize dabrafenib’s place among currently available melanoma therapies, and describe its mechanism of action, pharmacologic properties, adverse events, and the milestone clinical trials leading to dabrafenib’s FDA approval.

Expert opinion: Dabrafenib is a key first-line therapy for V600-mutated advanced melanoma patients with high tumor burden, brain metastases and significant cancer symptoms, and also serves as an effective salvage therapy. The future of BRAF inhibitor therapy in melanoma is rapidly unfolding, particularly in terms of combination therapy possibilities both with other targeted therapies as well as with immunotherapy.

Keywords:

• advanced melanoma
• BRAF mutation
• dabrafenib
• GSK2118436
• V600E

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.