Multidisciplinary approach to brain metastasis from melanoma: the emerging role of systemic therapies

Melanoma brain metastases are common, difficult to treat, and carry a poor prognosis. Until recently, systemic therapy was ineffective. Local therapy (including surgery, stereotactic radiotherapy, and whole brain radiotherapy) was considered the only option for a chance of disease control in the brain, and was highly dependent on the patient's performance status and age, number and size of brain metastases, and the presence of extracranial metastases. Since 2010, three drugs have demonstrated activity in progressing or "active" brain metastases including the anti-CTLA4 antibody ipilimumab (phase II study of 72 patients), and the BRAF inhibitors dabrafenib (phase II study of 172 patients, both previously treated and untreated brain metastases) and vemurafenib (a pilot study of 24 patients with heavily pretreated brain metastases). The challenge and unanswered question for clinicians is how to sequence all the available therapies, both local and systemic, to optimize the patient's quality of life and survival. This is an area of intense clinical research. The treatment of patients with melanoma brain metastases should be discussed by a multidisciplinary team of melanoma experts including a neurosurgeon, medical oncologist, and radiation oncologist. Important clinical features that help determine appropriate first line therapy include single compared with solitary brain metastasis, resectablity, BRAF mutation status of melanoma, rate of progression/performance status, and the presence of extracranial disease.