Revisiting the role of systemic therapies in patients with metastatic melanoma to the CNS

The CNS is a common site of metastasis in patients with malignant melanoma. Locoregional control either with surgery or radiotherapy is first-line treatment for patients with brain metastasis should they be suitable candidates. For those patients who are not and those who progress after previous treatment, there is an unmet clinical need for effective systemic therapies. Systemic cytotoxics, such as temozolamide and fotemustine, have only modest activity, resulting in a median progression-free survival ranging from 1-2 months, in patients with metastatic melanoma to the brain. Newer systemic treatments such as vemurafenib and ipilimumab have been approved for the treatment of melanoma, but evidence regarding their activity in brain metastases is inconclusive due to the limited access of patients to clinical trials. This is now being revised and more data are emerging supporting the inclusion of patients with brain metastasis in trials. In this review, the authors present data regarding the efficacy of systemically administered therapies in patients with metastatic melanoma to the brain.