Targeted MAPK Pathway Inhibitors in Patients With Disseminated Pilocytic Astrocytomas

J Natl Compr Canc Netw. 2017 Aug;15(8):978-982. doi: 10.6004/jnccn.2017.0139.

Abstract

This report presents a series of 5 pediatric patients with disseminated pilocytic astrocytomas and frequent nonfusion activating mutations. Genetic variants in these patients' tumors include BRAF p.Val600Glu, BRAF p.Val600Asp, and KRAS p.Gly60_Gln62ins7. The 2 patients with BRAF-mutated tumors were treated with dabrafenib or a combination of dabrafenib plus trametinib. The patients had either near complete resolution of the primary tumor (BRAF p.Val600Glu) or a stable primary tumor (BRAF p.Val600Asp). Both patients showed improvement in leptomeningeal dissemination without significant toxicity. Genomic testing of disseminated pilocytic astrocytomas, particularly those arising at extracerebellar locations, may result in the identification of mutations associated with ERK/MAPK activation. Patients with these activating mutations may benefit from targeted therapies.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Antineoplastic Agents / therapeutic use*
  • Astrocytoma / diagnosis*
  • Astrocytoma / drug therapy*
  • Astrocytoma / metabolism
  • Biomarkers, Tumor
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Disease Progression
  • Female
  • Humans
  • Infant
  • MAP Kinase Signaling System / drug effects*
  • Magnetic Resonance Imaging
  • Male
  • Molecular Targeted Therapy*
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Protein Kinase Inhibitors