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

David S. Ziegler; Marie Wong; Chelsea Mayoh; Amit Kumar; Maria Tsoli; Emily Mould; Vanessa Tyrrell; Dong-Anh Khuong-Quang; Mark Pinese; Velimir Gayevskiy; Richard J. Cohn; Loretta M. S. Lau; Mark Reynolds; Michael C. Cox; Andrew Gifford; Michael Rodriguez; Mark J. Cowley; Paul G. Ekert; Glenn M. Marshall; Michelle Haber

doi:10.1038/s41416-018-0251-2

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

David S. Ziegler^*, Marie Wong, Chelsea Mayoh, Amit Kumar, Maria Tsoli, Emily Mould, Vanessa Tyrrell, Dong-Anh Khuong-Quang, Mark Pinese, Velimir Gayevskiy, Richard J. Cohn, Loretta M. S. Lau, Mark Reynolds, Michael C. Cox, Andrew Gifford, Michael Rodriguez, Mark J. Cowley, Paul G. Ekert, Glenn M. Marshall, Michelle Haber

^*Corresponding author for this work

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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.

Original language	English
Pages (from-to)	693-696
Number of pages	4
Journal	British Journal of Cancer
Volume	119
Issue number	6
DOIs	https://doi.org/10.1038/s41416-018-0251-2
Publication status	Published - 11 Sept 2018
Externally published	Yes

Bibliographical note

Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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Publisher version (open access)Final published version, 1.33 MBLicence: CC BY

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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. (2018). Brief Report: potent clinical and radiological response to larotrectinib in TRK fusion-driven high-grade glioma. British Journal of Cancer, 119(6), 693-696. https://doi.org/10.1038/s41416-018-0251-2

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title = "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.",

author = "Ziegler, {David S.} and Marie Wong and Chelsea Mayoh and Amit Kumar and Maria Tsoli and Emily Mould and Vanessa Tyrrell and Dong-Anh Khuong-Quang and Mark Pinese and Velimir Gayevskiy and Cohn, {Richard J.} and Lau, {Loretta M. S.} and Mark Reynolds and Cox, {Michael C.} and Andrew Gifford and Michael Rodriguez and Cowley, {Mark J.} and Ekert, {Paul G.} and Marshall, {Glenn M.} and Michelle Haber",

note = "Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2018",

month = sep,

day = "11",

doi = "10.1038/s41416-018-0251-2",

language = "English",

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Ziegler, DS, Wong, M, Mayoh, C, Kumar, A, Tsoli, M, Mould, E, Tyrrell, V, Khuong-Quang, D-A, Pinese, M, Gayevskiy, V, Cohn, RJ, Lau, LMS, Reynolds, M, Cox, MC, Gifford, A, Rodriguez, M, Cowley, MJ, Ekert, PG, Marshall, GM & Haber, M 2018, 'Brief Report: potent clinical and radiological response to larotrectinib in TRK fusion-driven high-grade glioma', British Journal of Cancer, vol. 119, no. 6, pp. 693-696. https://doi.org/10.1038/s41416-018-0251-2

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T2 - potent clinical and radiological response to larotrectinib in TRK fusion-driven high-grade glioma

AU - Ziegler, David S.

AU - Wong, Marie

AU - Mayoh, Chelsea

AU - Kumar, Amit

AU - Tsoli, Maria

AU - Mould, Emily

AU - Tyrrell, Vanessa

AU - Khuong-Quang, Dong-Anh

AU - Pinese, Mark

AU - Gayevskiy, Velimir

AU - Cohn, Richard J.

AU - Lau, Loretta M. S.

AU - Reynolds, Mark

AU - Cox, Michael C.

AU - Gifford, Andrew

AU - Rodriguez, Michael

AU - Cowley, Mark J.

AU - Ekert, Paul G.

AU - Marshall, Glenn M.

AU - Haber, Michelle

N1 - Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2018/9/11

Y1 - 2018/9/11

N2 - 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.

AB - 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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EP - 696

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 6

ER -

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

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