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

David S. Ziegler(Cancer Institute of New South Wales), Marie Wong(Garvan Institute of Medical Research), Chelsea Mayoh(UNSW Sydney), Amit Kumar(Peter MacCallum Cancer Centre), Maria Tsoli(UNSW Sydney), Emily Mould(UNSW Sydney), Vanessa Tyrrell(UNSW Sydney), Dong‐Anh Khuong‐Quang(Royal Children's Hospital), Mark Pinese(Garvan Institute of Medical Research), Velimir Gayevskiy(Garvan Institute of Medical Research), Richard J. Cohn(UNSW Sydney), Loretta M. S. Lau(Sydney Children's Hospital), Mark Reynolds(Loxo Oncology at Lilly (United States)), Michael C. Cox(Loxo Oncology at Lilly (United States)), Andrew J. Gifford(UNSW Sydney), Michael Rodriguez(Prince of Wales Hospital), Mark J. Cowley(Garvan Institute of Medical Research), Paul G. Ekert(Royal Children's Hospital), Glenn M. Marshall(UNSW Sydney), Michelle Haber(UNSW Sydney)
British Journal of Cancer
September 1, 2018
10.1038/s41416-018-0251-2
Cited by 114Open Access
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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.

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