The emergence of targeted therapies for cancers harboring specific gene fusions, such as NTRK fusions, has revolutionized treatment strategies. However, identifying these patients requires a proactive approach from oncologists. A new review summarizes the complex landscape of Tropomyosin receptor kinase (TRK) fusion detection and treatment, providing clinicians with a framework to integrate this knowledge into daily practice.
This isn't just about knowing the science; it's about translating that science into improved patient outcomes. What assays should we use? Which patients benefit the most? And how do we navigate the reimbursement hurdles associated with these advanced diagnostics? It's time for pragmatic solutions.
Clinical Key Takeaways
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- The PivotCurrent ESMO guidelines recommend molecular testing for actionable fusions in several cancers; this review emphasizes expanding that testing to rarer cancers where TRK fusions may be present.
- The DataTRK fusions occur in approximately 0.5-1% of solid tumors, but response rates to TRK inhibitors can exceed 75% in fusion-positive cases.
- The ActionImplement reflex NGS testing in advanced cancers where standard therapies have failed, regardless of tumor type, to screen for TRK fusions.
Identifying Patients for TRK Fusion Testing
The first question every oncologist faces: Which patients should be tested for TRK fusions? The answer is nuanced, but a good starting point is advanced cancers where standard therapies have failed or are not available. This approach aligns with the general principles of personalized medicine, where genomic information guides treatment decisions. While some guidelines, such as those from the National Comprehensive Cancer Network (NCCN), recommend NGS for various advanced cancers, they don't explicitly mandate it for all. This review pushes for a broader application, especially in rarer tumor types where TRK fusions might be unexpectedly present. Consider this: A patient with a rare sarcoma refractory to conventional chemotherapy could be a candidate. Don't limit yourself to common tumor types.
Choosing the Right Assay for TRK Fusion Detection
Several methods exist for detecting TRK fusions, each with its pros and cons. NGS is the gold standard, offering comprehensive detection of various fusions simultaneously. However, it's more expensive and has a longer turnaround time. Immunohistochemistry (IHC) is faster and cheaper but requires a validated antibody and may miss certain fusions. Fluorescence in situ hybridization (FISH) is another option, but it's less comprehensive than NGS. The review emphasizes that NGS should be the preferred method, especially in cases where IHC is negative or inconclusive. However, in resource-limited settings, IHC can serve as a useful initial screening tool.
Selecting TRK Inhibitors: A Practical Approach
Once a TRK fusion is identified, the next step is choosing the appropriate TRK inhibitor. Larotrectinib and entrectinib are the two FDA-approved options. Both have demonstrated high response rates in TRK fusion-positive cancers, but they differ in their pharmacokinetic profiles and central nervous system penetration. The review suggests considering entrectinib for patients with brain metastases due to its ability to cross the blood-brain barrier. However, it's crucial to monitor patients for potential side effects, such as dizziness and fatigue, which can be more pronounced with entrectinib. Furthermore, resistance to TRK inhibitors can emerge, necessitating re-biopsy and genomic analysis to identify mechanisms of resistance and guide subsequent treatment decisions.
Navigating Insurance and Cost for TRK Fusion Testing
The cost of NGS testing and TRK inhibitors can be substantial, creating financial barriers for patients. Many insurance companies require prior authorization for NGS, and coverage policies may vary. Oncologists must be prepared to advocate for their patients by providing detailed justifications for testing and treatment. This review highlights the importance of working with financial counselors and patient advocacy groups to navigate these challenges. Consider that a single NGS panel can cost several thousand dollars, and TRK inhibitors can exceed $20,000 per month. We need to be transparent with patients about these costs and explore all available options, including patient assistance programs and clinical trials.
Study Limitations
While the review provides a comprehensive overview of TRK fusions, it's important to acknowledge its limitations. It's a review, not a randomized controlled trial. The conclusions are based on the available literature, which may be subject to publication bias and heterogeneity. Furthermore, the optimal testing and treatment strategies for TRK fusions are still evolving, and more research is needed to refine our approach. We also need better data on long-term outcomes and resistance mechanisms. Finally, the review doesn't explicitly address the ethical considerations surrounding genomic testing, such as incidental findings and data privacy. These are important issues that clinicians should be aware of.
Integrating TRK fusion testing into your practice requires a systematic approach. Start by identifying patients who are most likely to benefit from testing, focusing on those with advanced cancers where standard therapies have failed. Implement a reflex NGS testing protocol to streamline the process and ensure that all eligible patients are tested. Develop a close working relationship with your pathology and genetics departments to facilitate timely and accurate results. Educate your staff about the importance of TRK fusion testing and the potential benefits of targeted therapies. Don't underestimate the administrative burden. Obtain prior authorization for NGS testing and TRK inhibitors to avoid delays in treatment. Finally, stay up-to-date on the latest research and guidelines to ensure that you are providing the best possible care for your patients.
LSF-8096554847 | December 2025
How to cite this article
Reed E. Actionable insights on tropomyosin receptor kinase (trk) fusions in cancer. The Life Science Feed. Published December 18, 2025. Updated December 18, 2025. Accessed January 31, 2026. .
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This summary was generated using advanced AI technology and reviewed by our editorial team for accuracy and clinical relevance.
References
- Drilon, A., Laetsch, T. W., Hyman, D. M., et al. (2018). Larotrectinib in TRK fusion-positive cancers in adults and children. *New England Journal of Medicine*, *378*(8), 731-739.
- Doebele, R. C., Drilon, A., Paz-Ares, L., et al. (2020). Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. *The Lancet Oncology*, *21*(2), 271-282.
- National Comprehensive Cancer Network. (2023). *NCCN Guidelines for Non-Small Cell Lung Cancer*. Retrieved from [NCCN Website]
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