Dramatic clinical and radiographic response to BRAF inhibition in a patient with progressive disseminated optic pathway glioma refractory to MEK inhibition

Pediatr Hematol Oncol. 2017 May;34(4):254-259. doi: 10.1080/08880018.2017.1360971. Epub 2017 Oct 17.

Abstract

While clinical and radiographic responses to agents targeting the mitogen-activated protein kinases (MAPK) pathway have been repor-ted in pediatric low-grade gliomas (LGG), early phase trials indicate refractoriness to these medications in some of these patients. We report a patient with disseminated LGG with the BRAFV600E mutation, which was refractory to selumetinib, a MEK inhibitor, but subsequently showed immediate clinical and radiographic response to dabrafenib, a BRAF inhibitor, with sustained effect for 9 months prior to clinical progression. In LGGs, treatment resistance to one agent targeting the MAPK pathway might not imply refractoriness to other agents targeting this pathway.

Keywords: BRAF inhibitor; MAPK pathway; MEK inhibitor; dabrafenib; low-grade glioma.

MeSH terms

  • Amino Acid Substitution
  • Benzimidazoles / administration & dosage*
  • Chemoradiotherapy*
  • Glioma* / enzymology
  • Glioma* / genetics
  • Glioma* / pathology
  • Glioma* / therapy
  • Humans
  • Imidazoles / administration & dosage*
  • Infant
  • Male
  • Mutation, Missense*
  • Optic Nerve Neoplasms* / enzymology
  • Optic Nerve Neoplasms* / genetics
  • Optic Nerve Neoplasms* / pathology
  • Optic Nerve Neoplasms* / therapy
  • Oximes / administration & dosage*
  • Proto-Oncogene Proteins B-raf* / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf* / genetics
  • Proto-Oncogene Proteins B-raf* / metabolism

Substances

  • AZD 6244
  • Benzimidazoles
  • Imidazoles
  • Oximes
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • dabrafenib