Practical instructions for testing and targeted therapy in adult patients with solid tumours with NTRK gene fusion in common clinical practice

Česká verzia

Authors: Tomáš Büchler ¹; Pavel Dundr ²; Jindřich Fínek ³; Igor Kiss ⁴; Radoslav Matěj ^5,6; Bohuslav Melichar ⁷; Michal Michal ^8,9 ; Luboš Petruželka ¹⁰
Authors place of work: Onkologická klinika 1. LF UK a Thomayerovy nemocnice, Praha ¹; Ústav patologie, 1. LF UK a VFN v Praze ²; Onkologická a radioterapeutická klinika FN Plzeň ³; Klinika komplexní onkologické péče MOÚ Brno ⁴; Oddělení patologie a molekulární medicíny, Thomayerova nemocnice, Praha ⁵; Ústav patologie, FN Královské Vinohrady, Praha ⁶; Onkologická klinika FN Olomouc ⁷; Šiklův ústav patologie, FN Plzeň ⁸; Bioptická laboratoř s. r. o., Plzeň ⁹; Onkologická klinika 1. LF UK a VFN Praha ¹⁰
Published in the journal: Klin Onkol 2020; 33(6): 414-419
Category: Review

Summary

Background: Tropomyosin receptor kinase inhibitors (TRKi) have been shown to produce a dramatic and long-lasting effect on tumours harbouring fusions of neurotrophic receptor tyrosine kinase (NTRK) genes. Due to the low incidence of these molecular aberrations in common types of solid adult tumours, the identification of patients eligible for the treatment with TRK inhibitors in routine clinical practice is a major challenge. The current methods for NTRK gene fusion testing include immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and several genomic assays using next-generation sequencing (NGS). After considering the characteristics of these tests, we recommend two-step testing for clinical practice in tumours with a low incidence of NTRK gene fusions. In the first step, a fresh or archival formalin fixed paraffin embedded (FFPE) sample is tested using a validated IHC method. If the IHC result is positive, verification using RNA-based should follow, preferably using fresh tissue sample. If fresh tissue biopsy cannot be obtained, e. g. due to a disproportionate risk or discomfort for the patient, an archival FFPE sample may be used for testing. For tumours with high incidence of NTRK gene fusions, we recommend upfront NGS sequencing. Larotrektinib is currently the only TRK inhibitor registered in the EU. Although entrektinib, another TRK inhibitor, is not yet registered in the EU, it is currently available in the Czech Republic within an Early Access Programme. Purpose: The aim of this paper is to provide concise and clear guidance on testing for the presence of NTRK gene fusions and indications for the treatment with TRK inhibitors in the routine clinical oncology practice.

Keywords:

neurotrophic receptor kinase – targeted molecular therapy – entrektinib – larotrektinib – neoplasms

Zdroje

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