Brief Report: Potent clinical and radiological response to larotrectinib in TRK fusion-driven high-grade glioma

Br J Cancer. 2018 Sep;119(6):693-696. doi: 10.1038/s41416-018-0251-2. Epub 2018 Sep 17.


Genes encoding TRK are oncogenic drivers in multiple tumour types including infantile fibrosarcoma, papillary thyroid cancer and high-grade gliomas (HGG). TRK fusions have a critical role in tumourigenesis in 40% of infant HGG. Here we report the first case of a TRK fusion-driven HGG treated with larotrectinib-the first selective pan-TRK inhibitor in clinical development. This 3-year-old girl had failed multiple therapies including chemotherapy and radiotherapy. Tumour profiling confirmed an ETV6-NTRK3 fusion. Treatment with larotrectinib led to rapid clinical improvement with near total resolution of primary and metastatic lesions on MRI imaging. This is the first report of a TRK fusion glioma successfully treated with a TRK inhibitor.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Child, Preschool
  • Female
  • Glioma / diagnostic imaging
  • Glioma / drug therapy*
  • Glioma / genetics
  • Glioma / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Neoplasm Grading
  • Oncogene Proteins, Fusion / genetics
  • Pyrazoles / administration & dosage*
  • Pyrazoles / therapeutic use
  • Pyrimidines / administration & dosage*
  • Pyrimidines / therapeutic use
  • Treatment Outcome
  • Whole Genome Sequencing


  • ETV6-NTRK3 fusion protein, human
  • Oncogene Proteins, Fusion
  • Pyrazoles
  • Pyrimidines
  • larotrectinib