Clinical response to dabrafenib plus trametinib in a pediatric ganglioglioma with BRAF p.T599dup mutation

Cold Spring Harb Mol Case Stud. 2021 Apr 8;7(2):a006023. doi: 10.1101/mcs.a006023. Print 2021 Apr.


In this follow-up report, we present updated information regarding a previously reported pediatric patient with a World Health Organization grade I ganglioglioma harboring a BRAF p.T599dup mutation (Cold Spring Harb Mol Case Stud 4: a002618). This patient, based on our initial finding, is receiving combination targeted therapy with a selective BRAF inhibitor (dabrafenib) plus MEK inhibitor (trametinib). The combination therapy was started after the patient experienced progressive tumor growth and worsening neurological symptoms, including visual changes, headaches, and peripheral neuropathy, despite 9 months of treatment with adjuvant chemotherapy (vinblastine). The patient has been receiving dabrafenib plus trametinib for 15 months and continues to have stable disease as well as improved neurological symptoms. Although combinatorial therapy targeting BRAF and MEK using dabrafenib and trametinib, respectively, is indicated for tumors harboring a BRAF p.V600E/K mutation, our report demonstrates efficacy of this combination in a non-V600E BRAF-mutated tumor. The identification of BRAF alterations may assist clinicians in determining alternative targeted treatment strategies, especially considering the paucity of effective treatments for primary brain tumors and the poor prognosis associated with many central nervous system (CNS) diagnoses. Additional case studies or larger cohort reports will continue to clarify the efficacy of BRAF and/or MEK inhibitors in patients whose tumors harbor a BRAF alteration.

Keywords: glioma; neoplasm of the central nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Cohort Studies
  • Female
  • Ganglioglioma / diagnostic imaging
  • Ganglioglioma / drug therapy*
  • Ganglioglioma / genetics*
  • Ganglioglioma / pathology
  • Humans
  • Imidazoles / therapeutic use*
  • Mutation*
  • Oximes / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf / genetics*
  • Pyridones / therapeutic use*
  • Pyrimidinones / therapeutic use*
  • Treatment Outcome


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