Rapid Clinical and Radiographic Response With Combined Dabrafenib and Trametinib in Adults With BRAF-Mutated High-Grade Glioma

J Natl Compr Canc Netw. 2018 Jan;16(1):4-10. doi: 10.6004/jnccn.2017.7032.

Abstract

BRAF V600E mutations have been successfully treated with targeted therapy in melanoma, non-small cell lung cancer, and thyroid cancer. Interestingly, these mutations have also been identified in a subset of pediatric and adult brain tumors, with several cases reportedly responding to targeted therapy. However, these reports have been limited to single-agent BRAF inhibitor therapy and recurrent disease. Herein, we report dramatic clinical and radiographic responses to combination dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) in 2 adults with high-grade gliomas (HGGs), with 1 patient treated in the first-line setting. These observations, together with prior case reports, advocate for routine screening of BRAF point mutations in adult HGGs, and suggest that treatment with dual-targeted therapy, even in newly diagnosed cases, is safe and effective.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biopsy
  • Child
  • Child, Preschool
  • Female
  • Glioma / diagnosis
  • Glioma / drug therapy*
  • Glioma / genetics*
  • Humans
  • Imidazoles / administration & dosage
  • Infant
  • Magnetic Resonance Imaging
  • Male
  • Molecular Targeted Therapy
  • Mutation*
  • Oximes / administration & dosage
  • Proto-Oncogene Proteins B-raf / genetics*
  • Pyridones / administration & dosage
  • Pyrimidinones / administration & dosage
  • Radiography
  • Treatment Outcome

Substances

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