The use of systemic therapies for the treatment of brain metastases in metastatic melanoma: opportunities and unanswered questions

Abstract

The development of brain metastases is common in patients with metastatic melanoma and heralds a particularly poor prognosis. The development of the immunological agent ipilimumab and targeted treatments such as the selective BRAF inhibitor vemurafenib have revolutionised the treatment of metastatic disease. Evidence from clinical trials suggest these drugs may be effective in the treatment of brain metastases from melanoma. However efficacy may be limited by a lack of penetration of the blood brain barrier (BBB) and by multi substrate efflux pumps expressed on the BBB. The role and sequencing of radiotherapy, both whole brain and stereotactic radiotherapy, is yet to be determined but combinations of radiotherapy and systemic therapies may further increase the effects of these drugs on brain metastases. Considering the impact of brain metastases on morbidity and mortality in metastatic melanoma, future research into systemic drug therapy for the treatment of brain metastases and improvements in BBB penetrance should be a priority.

Keywords: BRAF; Blood brain barrier; Brain metastases; Dabrafenib; Ipilimumab; Melanoma; Vemurafenib.