Rapid progression of intracranial melanoma metastases controlled with combined BRAF/MEK inhibition after discontinuation of therapy: a clinical challenge

J Neurooncol. 2016 Sep;129(3):389-393. doi: 10.1007/s11060-016-2196-8. Epub 2016 Jul 11.


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.

Keywords: Intracranial disease; Melanoma; Target therapy.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Brain Neoplasms* / diagnostic imaging
  • Brain Neoplasms* / enzymology
  • Brain Neoplasms* / secondary
  • Brain Neoplasms* / therapy
  • Humans
  • Imidazoles / therapeutic use
  • MAP Kinase Kinase Kinases / antagonists & inhibitors
  • MAP Kinase Kinase Kinases / metabolism*
  • Magnetic Resonance Imaging
  • Male
  • Melanoma / pathology*
  • Oximes / therapeutic use
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / metabolism*
  • Pyridones / therapeutic use
  • Pyrimidinones / therapeutic use


  • Imidazoles
  • Oximes
  • Protein Kinase Inhibitors
  • Pyridones
  • Pyrimidinones
  • trametinib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • MAP Kinase Kinase Kinases
  • dabrafenib