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

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 la...

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Bibliographic Details
Published in:British journal of cancer Vol. 119; no. 6; pp. 693 - 696
Main Authors: Ziegler, David S, Wong, Marie, Mayoh, Chelsea, Kumar, Amit, Tsoli, Maria, Mould, Emily, Tyrrell, Vanessa, Khuong-Quang, Dong-Anh, Pinese, Mark, Gayevskiy, Velimir, Cohn, Richard J, Lau, Loretta M S, Reynolds, Mark, Cox, Michael C, Gifford, Andrew, Rodriguez, Michael, Cowley, Mark J, Ekert, Paul G, Marshall, Glenn M, Haber, Michelle
Format: Journal Article
Language:English
Published: England Nature Publishing Group 11.09.2018
Subjects:
Babies
Brain cancer
Brain Neoplasms - diagnostic imaging
Brain Neoplasms - drug therapy
Brain Neoplasms - genetics
Brain Neoplasms - pathology
Brain research
Cancer therapies
Chemotherapy
Child, Preschool
Female
Fibrosarcoma
Genomes
Genomics
Glioma
Glioma - diagnostic imaging
Glioma - drug therapy
Glioma - genetics
Glioma - pathology
Hospitals
Humans
Magnetic Resonance Imaging
Medical research
Metastases
Metastasis
Neoplasm Grading
Oncogene Proteins, Fusion - genetics
Papillary thyroid cancer
Patients
Pediatrics
Pyrazoles - administration & dosage
Pyrazoles - therapeutic use
Pyrimidines - administration & dosage
Pyrimidines - therapeutic use
Radiation therapy
Thyroid cancer
Treatment Outcome
Tumorigenesis
Tumors
Vomiting
Whole Genome Sequencing
ISSN:0007-0920, 1532-1827, 1532-1827
Online Access:Get full text
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Summary: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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ISSN:0007-0920
1532-1827
1532-1827
DOI:10.1038/s41416-018-0251-2