Biomarker NTRK Coverage from Every Angle
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NTRK Gene Fusion Analysis: Real-World Database of Patients With Cancer

By: Vanessa A. Carter, BS
Posted: Thursday, August 26, 2021

Filippo de Braud, MD, of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, and colleagues conducted a study to develop a large, real-world database of genomic profiling data to identify the prevalence and genomic landscape of NTRK gene fusions. Published in npj Precision Oncology, their findings concluded that NTRK fusions do not generally co-occur with other oncogenic drivers but instead revealed 88 unique fusion partners.

The data of nearly 300,000 patients from the FoundationCORE database were analyzed to pinpoint cancer types and histologies, co-occurrence with relevant oncogenic drivers and biomarkers, NTRK fusion prevalence, and gene fusion partners. To establish whether these cases were representative of the real-world population, these data were compared with those from patients enrolled in phase I or II clinical trials of the TRK inhibitor entrectinib (ALKA-372-001, STARTRK-1, and STARTRK-2.

Among 295,676 patients, 889 individuals were found to have an NTRK gene fusion. The prevalence of these mutations was found to decrease with age, presenting in 0.28% of adults and 2.28% of children younger than age 5. Notably, fusions in adults were mostly observed in salivary gland tumors, thyroid cancers, and soft-tissue sarcomas; pediatric patients also exhibited fusions most commonly in salivary gland tumors, along with solitary fibrous and breast tumors.

A total of 88 unique fusion partner pairs were uncovered, and a majority (65.9%), according to the authors, had never been previously reported in any large population study or database. ETV6-NTRK3 fusions appeared to be the most common fusion in both pediatric (32.7%) and adult (26.4%) patients, encompassing 36.8% of salivary gland tumors. Of note, these NTRK fusions were found to occur independently of disease-specific driver mutations.

“The results presented here deepen our general understanding of NTRK fusion–positive cancers and might help clinicians to identify patients potentially suitable for NTRK-directed therapies,” the study authors concluded.

Disclosure: For full disclosures of the study authors, visit nature.com.



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