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1Onkológiai Osztály, Magyar Honvédség Egészségügyi Központ, Budapest, Hungary. edina.kiss.dobos@gmail.com.
Abstract:
Tumor agnostic therapies target specific genomic alterations regardless of tumor localization and histological subtype. Neurotrophic tropomyosin receptor tyrosine kinase (NTRK) gene fusions are important driver gene targets in both pediatric and adult tumors. The first generation TRK inhibitors provide a rapid, effective, and long-lasting antitumor effect with a favorable side effect profile through selective inhibition of TRK fusion proteins. In the case report, we present a case of a young adult female patient with soft tissue sarcoma, in whom the multiple recurrent lower limb tumor disseminated after 3 years, but the systemic treatments used did not show a meaningful therapeutic response. Molecular diagnostic method confirmed the translocation of a very rare driver oncology target, the neurotrophic tropomyosin receptor tyrosine kinase 3 gene. We used convenient and safe inhibitor of tropomyosin receptor tyrosine kinase larotrectinib therapy with good efficacy and excellent quality of life. Larotrectinib was the first and only systemic therapy to which this metastatic soft tissue tumor responded.
Insights
Tumor agnostic therapies, targeting neurotrophic tropomyosin receptor tyrosine kinase (NTRK) gene fusions, show promise. Larotrectinib effectively treated a rare metastatic soft tissue sarcoma with NTRK3 gene fusion.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genomics
Background:
- Tumor agnostic therapies offer new treatment avenues by targeting specific genomic alterations.
- Neurotrophic tropomyosin receptor tyrosine kinase (NTRK) gene fusions are recognized as crucial driver oncogenes in various adult and pediatric malignancies.
- First-generation TRK inhibitors demonstrate rapid, effective, and durable antitumor responses with a favorable safety profile.
Observation:
- A young adult female presented with a disseminated, recurrent soft tissue sarcoma of the lower limb.
- Previous systemic treatments failed to yield a significant therapeutic response.
- Molecular diagnostics identified a rare neurotrophic tropomyosin receptor tyrosine kinase 3 (NTRK3) gene fusion.
Findings:
- Larotrectinib, a tropomyosin receptor tyrosine kinase inhibitor, was administered.
- The therapy demonstrated good efficacy and improved the patient's quality of life.
- Larotrectinib was the sole systemic treatment to which the metastatic soft tissue tumor responded.
Implications:
- This case highlights the clinical utility of tumor agnostic therapies in rare NTRK-driven sarcomas.
- Molecular profiling is essential for identifying targetable genomic alterations, such as NTRK gene fusions.
- Larotrectinib represents a viable and effective treatment option for patients with NTRK-altered metastatic cancers.