title: Systemic therapies for melanoma brain metastases: which drug for whom and when?
abstract: Melanoma brain metastases are common, difficult to treat, and are associated with a poor prognosis. Historically, due to the poor activity of chemotherapeutic agents in melanoma, the management of brain metastases was centred on local treatments such as surgery, stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT) depending on the clinical presentation. New systemic therapies have now evolved; kinase inhibitors targeting BRAF mutated melanoma cells and activating checkpoint inhibitors that activate an immune anti-tumour response, resulting in significantly improved survival and quality of life for patients with metastatic melanoma and these drugs have demonstrated activity in melanoma brain metastases. As the landscape shifts to incorporate these new systemic agents with the available local therapies, further research into using appropriate combinations or sequences of various treatments, especially for active or progressing melanoma brain metastasis, is required. This review will examine the evidence for systemic therapies in patients with active melanoma brain metastasis (untreated or treated and progressed) and highlight active and evolving clinical trials in this challenging field.
authors.affiliation: Melanoma Institute Australia, Sydney, Australia.
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Ramanujam
authors.affiliation: University Hospital Essen, Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.affiliation: Melanoma Institute Australia and The University of Sydney, 40 Rocklands Rd, North Sydney, NSW 2060, Australia. georgina.long@sydney.edu.au.
authors.forename: Georgina V
authors.initials: GV
authors.lastname: Long
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000556:secondary*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000556:secondary*; D025202:Molecular Diagnostic Techniques; D058990:Molecular Targeted Therapy; D009154:Mutation; D018579:Patient Selection; D010641:Phenotype; D057285:Precision Medicine; D011237:Predictive Value of Tests; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: BRAF; Melanoma; brain metastases; drug; systemic therapy