Advances in the Systemic Treatment of Melanoma Brain Metastases

It is estimated that up to 40% of patients with distantly metastatic melanoma develop clinically detectable brain metastases. The prognosis for these patients is very poor with an historical median overall survival of approximately 4 months. Targeted surgical and radiotherapy-based approaches can improve outcomes in certain patients. Over the past decade, the efficacy of systemic treatments for metastatic melanoma has improved with the development of anti-CTLA-4 and anti-PD-1-based immunotherapies (checkpoint inhibitors) that provide survival benefit. In patients whose melanoma expresses a V600 BRAF mutation which activates the MAPK signaling pathway, the targeted inhibition of BRAF and MEK also confers survival benefit. These immunomodulatory and molecular-targeted approaches have recently been studied in patients with melanoma brain metastases to determine efficacy of these approaches in treating the brain metastases. Advances in use of chemotherapy, immune checkpoint inhibitors, and BRAF plus MEK inhibitors to treat melanoma brain metastases are discussed.