Related Experiment Video
Updated: Sep 7, 2025
Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
Timing of NTRK Gene Fusion Testing and Treatment Modifications Following TRK Fusion Status Among US Oncologists
Andrew J Klink1, Abhishek Kavati2, Awa T Gassama2
1Cardinal Health, Dublin, Ohio, USA. andrew.klink@cardinalhealth.com.
Background:
Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers with an estimated prevalence of less than 1% across all solid tumors. Tropomyosin receptor kinase inhibitors (TRKis) block the constitutively activated tyrosine receptor kinase (TRK) fusion protein produced in NTRK gene fusion positive (NTRK+) tumors from downstream signaling. Tropomyosin receptor kinase inhibitors are now first-line (1L) or subsequent treatment options for TRK fusion cancers.
Objective:
This study assessed timing of NTRK gene fusion testing and treatment modifications among patients with TRK fusion cancers.
Patients And Methods:
This was a one-time physician questionnaire with a retrospective, multisite patient chart abstraction of oncology practices in the USA. From June to September 2020, medical oncologists from the Oncology Provider Extended Network (OPEN) who treated patients with NTRK+ advanced/metastatic solid tumors abstracted information into electronic case report forms (eCRFs) for adult patients with advanced/metastatic solid tumors and a NTRK+ tumor test result with a known fusion partner. Use of NTRK testing in routine clinical practice among patients with advanced/metastatic solid tumors was assessed. Data included demographic, clinical, and NTRK gene fusion testing characteristics. Responses were summarized using descriptive statistics.
Results:
Twenty-eight community-based medical oncologists who had managed or treated 148 patients with advanced/metastatic TRK fusion cancer between 01/01/2016 and 12/31/2019 completed the survey. Lung (27%), thyroid (18%), salivary gland (14%), and colorectal (12%) were the most commonly reported tumor types. A majority (68%) tested NTRK status prior to 1L initiation; testing after disease progression on 1L (36%), 2L (25%), and 3L (21%) was also noted. Most oncologists (96%) reported no difficulty interpreting NTRK reports. Nearly all (96%) indicated using next-generation sequencing (NGS) for determining NTRK status. The majority (57%) indicated that age, tumor type, and performance status did not impact NTRK testing decisions. Less than half (46%) include TRKi therapy following NTRK+ determination. NTRK testing guidelines were commonly reviewed by physicians (89%).
Conclusion And Relevance:
Among patients with advanced/metastatic TRK fusion cancer, medical oncologists reported testing for NTRK fusions at diagnosis or prior to 1L. Future research should elucidate why fewer than half of oncologists surveyed (46%) would not use TRKis after NTRK+ status confirmation, assess clinical practices among NTRK+ patients, and characterize treatment patterns and clinical outcomes in real-world settings.
Insights
Most oncologists test for NTRK gene fusions before first-line treatment, but less than half use tropomyosin receptor kinase inhibitors (TRKIs) after confirmation. Further research is needed on TRKI use in NTRK fusion cancers.
Area of Science:
- Oncology
- Molecular Diagnostics
- Cancer Therapeutics
Background:
- Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are rare oncogenic drivers in solid tumors.
- Tropomyosin receptor kinase inhibitors (TRKIs) target TRK fusion proteins in NTRK gene fusion-positive (NTRK+) cancers.
- TRKIs are established treatment options for TRK fusion cancers.
Purpose of the Study:
- To assess the timing of NTRK gene fusion testing in routine clinical practice.
- To evaluate treatment modifications and the use of TRKIs in patients with NTRK+ advanced/metastatic solid tumors.
Main Methods:
- Retrospective, multisite physician questionnaire and patient chart abstraction.
- Data collected from 28 community-based medical oncologists on 148 patients (01/01/2016–12/31/2019).
- Assessed NTRK testing practices, fusion partners, tumor types, and TRKI utilization.
Main Results:
- A majority of oncologists (68%) tested NTRK status before first-line (1L) therapy; testing also occurred after 1L, 2L, and 3L progression.
- Lung, thyroid, salivary gland, and colorectal cancers were the most common NTRK+ tumor types.
- While 96% used next-generation sequencing (NGS) for testing, only 46% reported using TRKi therapy after NTRK+ confirmation.
Conclusions:
- NTRK gene fusion testing is often performed at diagnosis or before 1L therapy.
- A significant gap exists between NTRK+ status confirmation and TRKi treatment initiation.
- Further research is warranted to understand barriers to TRKi use and real-world outcomes in NTRK fusion cancers.
More Related Videos
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:56Treatment Resistant Cancers
01:00Enzyme-linked Receptors
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...