title: Rapid progression of intracranial melanoma metastases controlled with combined BRAF/MEK inhibition after discontinuation of therapy: a clinical challenge.
abstract: Novel systemic therapies with anti-tumor activity in the brain including small molecules targeting BRAF and MEK, and immune checkpoint inhibition, offer the possibility of improved control of intracranial disease. A number of prospective trials support the judicious use of modern systemic therapies in patients with melanoma and limited brain metastases .The intracranial clinical course of patients who progress extracranially on BRAF/MEK inhibition remains poorly described in the literature. In this report, we highlight a series of clinical cases, with rapid progression of intracranial disease following discontinuation of dabrafenib/trametinib for extracranial disease progression or toxicity, a previously unreported finding in the medical literature with significant implications for patient care.
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA. dcagney@lroc.harvard.edu.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Cagney
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Alexander
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Elizabeth I
authors.initials: EI
authors.lastname: Buchbinder
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Ott
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
authors.forename: Ayal A
authors.initials: AA
authors.lastname: Aizer
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000201:enzymology / Q000556:secondary / Q000628:therapy; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008545:Melanoma / Q000473:pathology*; D010091:Oximes / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011728:Pyridones / Q000627:therapeutic use; D011744:Pyrimidinones / Q000627:therapeutic use
chemical_list: D007093:Imidazoles; D010091:Oximes; D047428:Protein Kinase Inhibitors; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020930:MAP Kinase Kinase Kinases; C561627:dabrafenib
keywords: Intracranial disease; Melanoma; Target therapy