Dabrafenib in the treatment of advanced melanoma

Abstract

Advanced melanoma has long been a challenging malignancy to treat due to a relative paucity of efficacious therapeutic options. However, the identification of activating BRAF mutations in approximately 50% of patients with cutaneous melanoma has ushered in the era of targeted therapy for melanoma patients. Similar to the first-in-class selective serine/threonine-protein kinase B-raf inhibitor vemurafenib, dabrafenib is highly efficacious in melanoma patients with BRAF V600E mutations, with response rates of approximately 50% and progression-free survival of 6 months. There is data to suggest that dabrafenib not only shows activity in V600E-mutated melanoma, but also in non-V600E BRAF-mutated disease such as V600K. There is also early data to suggest that dabrafenib is effective in controlling metastases in the brain. Combining dabrafenib with the selective mitogen-activated protein kinase kinase (MEK) inhibitor trametinib has been effective in improving both the progression-free survival and overall survival of melanoma patients over those patients treated with dabrafenib alone. Dabrafenib is still being evaluated in several clinical trials in melanoma as well as a variety of other solid tumors with BRAF mutations. The U.S. Food and Drug Administration has recently approved dabrafenib as a single agent for the treatment of unresectable or metastatic melanoma in adult patients with BRAF V600E mutation.

Keywords: BRAF; Dabrafenib; Melanoma; Targeted therapy.