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

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.

Type Journal
ISBN 0007-0920
Authors Ziegler, D. S.; Wong, M.; Mayoh, C.; Kumar, A.; Tsoli, M.; Mould, E.; Tyrrell, V.; Khuong-Quang, D. A.; Pinese, M.; Gayevskiy, V.; Cohn, R. J.; Lau, L. M. S.; Reynolds, M.; Cox, M. C.; Gifford, A.; Rodriguez, M.; Cowley, M. J.; Ekert, P. G.; Marshall, G. M.; Haber, M.
Responsible Garvan Author Dr Mark Cowley
Publisher Name British Journal of Cancer
Published Date 2018-09-17
Status Published in-print
DOI 10.1038/s41416-018-0251-2