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: London Nature Publishing Group UK 11.09.2018
Nature Publishing Group
Subjects:
631/67/1059/602
631/67/1922
Babies
Biomedical and Life Sciences
Biomedicine
Brain cancer
Brain Neoplasms - diagnostic imaging
Brain Neoplasms - drug therapy
Brain Neoplasms - genetics
Brain Neoplasms - pathology
Brain research
Brief Communication
Cancer Research
Cancer therapies
Chemotherapy
Child, Preschool
Drug Resistance
Epidemiology
Female
Fibrosarcoma
Genomes
Genomics
Glioma
Glioma - diagnostic imaging
Glioma - drug therapy
Glioma - genetics
Glioma - pathology
Hospitals
Humans
Magnetic Resonance Imaging
Medical research
Metastases
Metastasis
Molecular Medicine
Neoplasm Grading
Oncogene Proteins, Fusion - genetics
Oncology
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