Recent advances in the treatment of melanoma with BRAF and MEK inhibitors

Abstract

Selective inhibition of the mitogen activated protein kinase (MAPK) pathway with either BRAF or MEK inhibition has emerged as the key component for the treatment of BRAF-mutant metastatic melanoma. New evidence from several phase III trials suggests that the combination of BRAF and MEK inhibitors improves tumor response rate and progression-free survival (PFS). Some of the serious adverse events, in particular, the incidence of cutaneous squamous cell carcinoma seen with the monotherapy treatment with a BRAF inhibitor are attenuated with combination therapy, whereas milder side effects such as pyrexia can be more common with combination therapy. Although dose reductions and dose interruptions are slightly more common with combination therapy, overall data supports the notion that combination therapy is safe and improves the outcomes for metastatic melanoma patients compared to single agent BRAF inhibitors.

Keywords: BRAF inhibitor; BRAF mutation; MEK inhibitor; Metastatic melanoma; NRAS mutation.

Figure 1

MAPK pathway. RTK, receptor tyrosine kinase; GTP, guanosine triphosphate; ERK, extracellular signal-related kinase; MAP, mitogen-activated protein; MAPK, mitogen-activated protein kinase.

Figure 2

Mechanisms of resistance to BRAF inhibitors.

Figure 3

Acquired resistance to BRAF inhibitors.