Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies

The development of selective BRAF inhibitors in patients with metastatic BRAF V600 mutant melanoma has proven to be an effective therapeutic strategy. While vemurafenib was the first approved BRAF inhibitor for this indication, another selective BRAF inhibitor, dabrafenib, has demonstrated efficacy in patients with BRAF mutant melanoma, including those with active brain metastases and other malignancies.

This review covers the current role of BRAF inhibitors in patients with metastatic melanoma and the clinical development of dabrafenib. The pharmacological, safety and efficacy data are discussed from the Phases I, II and III studies of dabrafenib. In addition, the results of the Phase II study of dabrafenib in melanoma patients with active brain metastases (BREAK-MB) and the Phase I/II study of dabrafenib/trametinib are examined.

While dabrafenib has demonstrated comparable efficacy to vemurafenib in BRAF V600E mutant melanoma patients, the BREAK-MB and dabrafenib/trametinib studies have taken BRAF inhibitor strategies further with evidence of disease activity in patients with metastatic melanoma brain metastases and potential abrogation of BRAF inhibitor resistance.