Melanoma Brain Metastases: An Update on the Use of Immune Checkpoint Inhibitors and Molecularly Targeted Agents.

Brain metastases from melanoma are no longer uniformly associated with dismal outcomes. Impressive tumor tissue-based (craniotomy) translational research has consistently shown that distinct patient subgroups may have a favorable prognosis. This review provides a historical overview of the standard-of-care treatments until the early 2010s. It subsequently summarizes more recent advances in understanding the biology of melanoma brain metastases (MBMs) and treating patients with MBMs, mainly focusing upon prospective clinical trials of BRAF/MEK and PD-1/CTLA-4 inhibitors in patients with previously untreated MBMs. These additional systemic treatments have provided effective complementary treatment approaches and/or alternatives to radiation and craniotomy. The current role of radiation therapy, especially in conjunction with systemic therapies, is also discussed through the lens of various retrospective studies. The combined efficacy of systemic treatments with radiation has improved overall survival over the last 10 years and has sparked considerable research interest regarding optimal dosing and sequencing of radiation treatments with systemic treatments. Finally, the review describes ongoing clinical trials in patients with MBMs.