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AACR 2023: Concordance Between Tissue-Based Testing Methods for Identifying NTRK Gene Fusion

By: Amy MacDonald, MS
Posted: Tuesday, May 16, 2023

Erin R. Rudzinski MD, of the University of Washington Medical Center, Seattle, and colleagues examined the concordance between NTRK gene fusion data obtained from solid tumor biopsy compared with liquid tumor biopsy, measuring circulating tumor DNA (ctDNA). Presented at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Abstract CT228/18), their results demonstrated agreement between NTRK gene fusion data extracted from tumor tissue itself compared with fusion data obtained from ctDNA.

NTRK gene fusions lead to transcription of chimeric TRK proteins with constitutively activated or overexpressed kinases, leading to oncogenic transformation. Larotrectinib is a highly selective TRK inhibitor used to treat solid tumors with NTRK gene fusions. Because larotrectinib selectively targets tumors with such fusions, accurate detection of NTRK gene fusions across many tumor types is warranted.

The researchers examined patient data from three larotrectinib clinical trials ( identifier NCT02122913, NCT02576431, and NCT02637687). Of the 164 patients with NTRK fusions identified by local testing, 117 had evaluable tissue samples for central testing, and 99 had evaluable liquid biopsy samples. Tumor NTRK gene fusion status was determined locally by a variety of methods and centrally by next-generation sequencing in both tissue (using Illumina TruSight Oncology Comprehensive) and ctDNA (using Guardant360 or GuardantOMNI) at baseline. In total, 81.2% (95 of 117) of tumors had their fusions confirmed by central tissue testing. Use of ctDNA testing detected NTRK gene fusions in 33.3% (33 of 99) of patients.

The researchers concluded that a high proportion of tumors with NTRK gene fusions identified through tumor biopsy were also confirmed when ctDNA was assessed. However, analysis of ctDNA was found to be less sensitive at detecting NTRK gene fusions overall, leading the researchers to recommend that negative ctDNA results be reexamined using next-generation sequencing testing of tissue biopsies.

Disclosure: For full disclosures of study authors, visit

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