Abstract 1693P
Background
Oncogenic fusion of neurotrophin receptor tyrosine kinase NTRK1, NTRK2, or NTRK3 genes have been found in different types of solid tumours. Nevertheless, the incidence of NTRK gene fusions in these cancers remains quite unexplored. The treatment of patients with TRK fusion cancer with a first-generation TRK inhibitor (such as larotrectinib or entrectinib) is associated with high response rates (>75%), regardless of tumour histology and presence of metastases, and acceptable toxicity profile. Due to the efficacy of TRK inhibitor therapy and the recent Food and Drug Administration and European Medicines Agency approval of larotrectinib and entrectinib, it is clinically important to identify patients accurately and efficiently with TRK fusion cancer. In this study, we provide unique data on the incidence of oncogenic NTRK gene fusions in adult patients with brain metastases (BM) and gliomas.
Methods
In this study, 140 samples fixed and paraffin-embedded tissue (FFPE) of adult patients with gliomas (60 whose 19 of WHO grade II, 21 of WHO grade III and 20 glioblastomas) and BM (80 with different primary tumours) are analysed. Identification of NTRK gene fusions is performed using next-generation sequencing (NGS) technology on the Ion Torrent S5XL automaton with the Oncomine Focus RNA assay kit (ThermoFisher). The analysis is carried out using the Ion Reporter software. A minimum of 50,000 mapped reads is required to allow interpretation of the result.
Results
Among the first 47 samples (30 gliomas and 17 BM) analysed, a NTRK3 gene fusion was identified in a WHO grade II glioma sample. Another 93 samples are to be analysed. These are composed of 63 BM and 30 gliomas.
Conclusions
Due to the size of the population analysed, this study will provide pioneering data on the incidence of NTRK gene fusions in brain tumors, which could strongly support the relevance of innovative clinical trials with specific targeted therapies (larotectinib, entrectinib) in this patients's population.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Groupement de Coopération Sanitaire Ramsay Santé pour l'Enseignement et la Recherche.
Funding
Bayer HealthCare SAS-Pharmaceuticals.
Disclosure
All authors have declared no conflicts of interest.