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Belgian expert consensus for tumor-agnostic treatment of NTRK gene fusion-driven solid tumors with larotrectinib
Ahmad Awada1, Thierry Berghmans2, Paul M Clement3
1Oncology Medicine Department, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium.
Abstract:
Fusions of NTRK (neurotrophic tyrosine receptor kinase) genes with 5' partner genes can result in the expression of chimeric proteins that drive oncogenesis through ligand-independent kinase activation. Despite variable frequencies of NTRK fusions in different tumor types, the fact that they are common to a wide range of cancers raises the possibility of developing tumor-agnostic treatments specifically targeting NTRK fusion products, irrespective of tumor type. The first-generation Trk (tropomyosin receptor kinase) inhibitor, larotrectinib, was the first tumor-agnostic treatment of NTRK fusion-positive cancers in adults and children, to be approved in the European Union. This consensus, developed by a Belgian multidisciplinary expert panel, aims to highlight the unmet medical need associated to NTRK fusion-driven cancer treatment and, based on current knowledge of NTRK fusions and larotrectinib treatment outcome and safety, provide comprehensive guidance to oncologists regarding NTRK fusion-driven cancer diagnostics and the best use of larotrectinib in real-world clinical settings.
Insights
Neurotrophic tyrosine receptor kinase (NTRK) gene fusions drive cancer. Larotrectinib offers a tumor-agnostic treatment for NTRK fusion-positive cancers, guiding oncologists on its use.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers.
- These fusions occur across various cancer types, suggesting a common therapeutic target.
- Targeting NTRK fusions offers a potential for tumor-agnostic cancer therapies.
Purpose of the Study:
- To address the unmet need in treating NTRK fusion-driven cancers.
- To provide guidance on diagnosing NTRK fusions.
- To outline the optimal use of larotrectinib in clinical practice.
Main Methods:
- Multidisciplinary expert panel consensus development.
- Review of current knowledge on NTRK fusions.
- Analysis of larotrectinib treatment outcomes and safety data.
Main Results:
- Larotrectinib is the first approved tumor-agnostic therapy for NTRK fusion-positive cancers.
- Established diagnostic approaches for NTRK fusions.
- Provided evidence-based recommendations for larotrectinib use.
Conclusions:
- NTRK fusions represent a targetable driver across diverse malignancies.
- Larotrectinib demonstrates efficacy as a tumor-agnostic treatment.
- This consensus provides essential guidance for oncologists managing these rare genetic alterations.
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