Annotation Detail

Information
Associated Genes
NTRK1
Associated Variants
NTRK1 TMP3-NTRK1 NTRK1 TMP3-NTRK1
Associated Disease
sarcoma
Source Database
CIViC Evidence
Description
Four patients with infantile fibrosarcoma and soft tissue sarcoma and a NTRK1-TMP3 fusion were treated with larotrectinib. Two had a partial, and two had a complete response. Treatment was done within a multicentre, open-label, phase 1/2 study and enrolled infants, children, and adolescents aged 1 month to 21 years with locally advanced or metastatic solid tumours or CNS tumours that had relapsed, progressed, or were non-responsive to available therapies regardless of TRK fusion Status. In total, 24 patients (n=17 with tumours harbouring TRK fusions, n=7 without a documented TRK fusion) were enrolled. Among the fusion-positive patients, eight (47%) had infantile fibrosarcoma, seven (41%) had other soft tissue sarcomas, and two (12%) had papillary thyroid cancer. 14 (93%) of 15 patients with TRK fusion-positive cancers achieved an objective response; the remaining patient had tumour regression that did not meet the criteria for objective response. None of the seven patients with TRK fusion-negative cancers had an objective response.
Variant Origin
N/A
Variant Origin
N/A
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/6101
Gene URL
https://civic.genome.wustl.edu/links/genes/3983
Variant URL
https://civic.genome.wustl.edu/links/variants/2288
Rating
4
Evidence Type
Predictive
Disease
Sarcoma
Evidence Direction
Supports
Drug
Larotrectinib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
29606586
Drugs
Drug NameSensitivitySupported
LarotrectinibSensitivitytrue