Journal article
Brief Report: Potent clinical and radiological response to larotrectinib in TRK fusion-driven high-grade glioma
DS Ziegler, M Wong, C Mayoh, A Kumar, M Tsoli, E Mould, V Tyrrell, DA Khuong-Quang, M Pinese, V Gayevskiy, RJ Cohn, LMS Lau, M Reynolds, MC Cox, A Gifford, M Rodriguez, MJ Cowley, PG Ekert, GM Marshall, M Haber
British Journal of Cancer | NATURE PUBLISHING GROUP | Published : 2018
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 gli..
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Funding Acknowledgements
The brain tumour precision medicine program was funded by the Cure Brain Cancer Foundation. Whole-Genome Sequencing was funded by the Australian Lions Childhood Cancer Research Foundation and Lions Club International Foundation (LCIF) as part of the Lions Kids Cancer Genome Project. AK and VT's salaries were supported by the CRC for Cancer Therapeutics, EM's salary was supported by The Kids Cancer Project, LL's and CM's salary were supported by Cancer Institute NSW, and MJC's salary was supported by NSW Department of Health Early-Mid Career Fellowship. DK is the Herman Clinical Fellow at the University of Melbourne. The Zero Childhood Cancer Program has also been supported by the Commonwealth Government of Australia, The NSW State Government, University of NSW, Tour de Cure, The Rich Family Foundation, the Robert Connor Dawes Foundation, and The Lenity Foundation.