NTRK3 fusion

This case illustrates an example of pediatric precision oncology in a neonate with an ETV6::NTRK3 (+) congenital IFS of the head and neck region and provides further reference for the use of larotrectinib in the neonatal period.

After receiving dacomitinib and almonertinib sequentially, plasma-based NGS revealed the emergence of EGFR T790M-trans-C797S mutations, prompting a switch to a combination therapy of almonertinib and gefitinib...Larotrectinib was incorporated into the dual EGFR-TKI regimen, forming a triplet therapy...This is the first reported case of a novel, targetable POT1::NTRK3 fusion as a potential off-target mechanism mediating EGFR-TKI resistance, occurring alongside MET amplification in a patient with NSCLC harboring acquired EGFR L858R/T790M/C797S mutations. Concomitant inhibition of EGFR, NTRK, and MET was safe and resulted in a significant response, underscoring the importance of precision medicine guided by matched NGS.

There is little published literature to guide care for low-grade NTRK3 mutation STS. This case highlights the importance of multidisciplinary care for STS.

Herein we describe a patient with secretory carcinoma showing transdifferentiation into metaplastic carcinoma (spindle cell and squamous cell carcinoma) at the metastatic site following treatment. Identification of these morphologic shifts is crucial for accurate classification and identification of potential resistant mechanisms.

Following 1 month of entrectinib treatment, the patient experienced considerable tumor shrinkage and symptomatic improvement. For bone-derived NTRK-rearranged spindle cell sarcomas, entrectinib shows promising therapeutic efficacy and should be considered a preferred treatment option.

Since BRAF activation occurs in BRAF fusion gene tumors and BRAF mutations, they could share a similar mechanism in tumorigenesis. This case suggests the further expansion of kinase-related spindle cell tumors.

In this limited case series, two patients were dead at the last follow-up. Whether these findings are consistent within this patient population remains to be addressed as more patient series are published.

P1/2, N=450, Recruiting, DualityBio Inc. | N=280 --> 450 | Trial completion date: Apr 2025 --> Sep 2026 | Trial primary completion date: Apr 2025 --> Sep 2026

The fusion involved STRN3 (exon-3) and NTRK3 (exon-14) genes and was identified through next-generation sequencing analysis. Recognizing this specific molecular rearrangement is crucial, as it not only enables targeted therapy but also holds diagnostic significance in specific clinical scenarios.

P2, N=31, Active, not recruiting, Children's Oncology Group | N=70 --> 31

Our standard operating procedure (SOP) was updated to perform orthogonal confirmation testing for stand-alone equivocal NTRK1/2 and equivocal NTRK3 (5' failure), but to ignore equivocal NTRK3 (5' intact) and report as NTRK2/3 indeterminate. Re-verification showed no change to ALK, ROS1, RET, MET ex14, and NTRK1 results. Sensitivity of NTRK2 detection was significantly increased (80% after orthogonal testing).

The routine use of RNA-based CGP analysis allows for the comprehensive detection of oncogenic fusions in patients with cancer. The diversity of tumor types in which actionable fusions were detected supports the broader utilization of CGP to potentially increase targeted therapy usage and improve outcomes across cancer subtypes.