Systemic Therapy for Brain Metastases: Melanoma

Brain metastases are a significant cause of morbidity and mortality in patients with advanced melanoma and constitute a therapeutic challenge. Systemic treatment targeting both mutant BRAF and immune checkpoints has revolutionized the management of metastatic melanoma and prolonged patient survival. However, the impact of these drugs on central nervous system metastases was less well understood as historically many clinical trials for melanoma excluded patients with brain metastases. As the field has progressed, multiple clinical trials focusing specifically on systemic therapy approaches for melanoma brain metastases have been completed or are underway. Although combined BRAF and MEK inhibition has now shown intracranial response rates of over 50%, responses appear to be less durable in the brain than in extracranial metastatic sites. Anti-PD-1 monotherapy and combined ipilimumab and nivolumab have intracranial response rates of over 20% and 50%, respectively, with concordant responses among brain and extracranial sites with clear durability. In this chapter, we discuss the results of clinical trials studying the use and combination of targeted agents and immunotherapy for melanoma brain metastases, local approaches such as stereotactic radiosurgery, and current challenges in the management of melanoma brain metastases.