Developments in therapy for brain metastases in melanoma patients.

: Cutaneous melanoma brain metastases (MBM) are a major cause of morbidity and mortality. While cytotoxic agents, interferon, or interleukin-2, have been used with some success in extracranial disease, limited efficacy is demonstrated in MBM. The rare patient with long-term survival presented with limited intracranial disease amenable to surgery or radiation therapy. However, the development of targeted therapy and immunotherapy over the last decade has significantly improved overall survival in this formerly devastating presentation of metastatic melanoma.: This article reviews the mechanism of brain metastasis, challenges with treating the central nervous system, historical treatment of MBM, and outcomes in clinical trials with targeted therapy and immunotherapy. The MBM patient population now, more than ever, requires a multidisciplinary approach with surgery, radiation therapy, and the use of newer systemic therapies such as immunotherapy agents and targeted therapy agents. MBM has traditionally been excluded from clinical trials for systemic therapy due to poor survival. However, recent data show overall survival rates have significantly improved, supporting the need for inclusion of MBM patients in systemic therapy clinical trials. Understanding the mechanisms of therapeutic activity in the brain, resistance  mechanisms, and the appropriate multi-modality treatment approach requires further investigation. Nevertheless, these therapies continue to give some hope to patients with historically poor survival.