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

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

Author information

1
Kids Cancer Centre, Sydney Children's Hospital, Randwick, NSW, Australia. d.ziegler@unsw.edu.au.
2
Children's Cancer Institute, UNSW, Sydney, NSW, Australia. d.ziegler@unsw.edu.au.
3
Kinghorn Centre for Clinical Genomics, Garvan Institute, Sydney, NSW, Australia.
4
Children's Cancer Institute, UNSW, Sydney, NSW, Australia.
5
Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
6
Murdoch Children's Research Institute, Royal Children's Hospital, The University of Melbourne, Melbourne, VIC, Australia.
7
Kids Cancer Centre, Sydney Children's Hospital, Randwick, NSW, Australia.
8
Clinical Development, Loxo Oncology, Inc., South San Francisco, San Francisco, CA, USA.
9
Department of Anatomical Pathology, Prince of Wales Hospital, Randwick, NSW, Australia.
10
St Vincent's Clinical School, UNSW Sydney, Sydney, NSW, Australia.

Abstract

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.

PMID:
30220707
PMCID:
PMC6173734
DOI:
10.1038/s41416-018-0251-2
[Indexed for MEDLINE]
Free PMC Article

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