Abstract 1312: A study of the clinical utility of NTRKs only vs. comprehensive gene fusion panel testing from a single assay platform

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Abstract Background: Gene fusions have important implications for therapeutic selection and patient quality of care, and though they have a low prevalence individually, many fusions are targeted effectively, agnostic of any tumor type. Unfortunately, patients in the community oncology setting are most often only tested for NTRK fusions, which have a prevalence of around 1%. Here, we compared side by side the actual clinical actionability differences using real-world testing data between broad vs. NTRK fusion only panels offered by our clinical laboratory, both with identical assay performance characteristics, reimbursement, and cost levels. Methods: Clinical samples(n=8307) from 33 tumor types were tested for known and novel RNA fusions using our hybridization capture RNA-seq based Solid Tumor Fusion Panels in our clinical laboratory, which targets RNA breakpoints at 1104 genes. Deidentified results were analyzed before or after filtering for fusions based on either a Targeted Solid Tumor NGS fusion Panel (16 drug targetable genes) or only NTRKs fusions. Deidentified patient data presented was analyzed according to an IRB-approved protocol. Results: The prevalence of fusions in the cohort was 30.5% involving any of the 1104 targeted genes by the assay (27% in frame, 20% out of frame, and 41% others). Druggable fusions were present in 5.1% (422) of patients, where 53% were female with a median age of 68 years old, and 47% were male with a median age of 70. However, when filtering only for NTRK fusions, only 104 patients had an NTRK fusion (38 NTRK1, 10 NTRK2, 56 NTRK3), while an additional 318 patients had detected fusions from the Targeted Panel. These druggable fusions had the following prevalences; ALK 0.6 %, BRAF 0.3%, FGFR1 0.2%, FGFR2 0.3%, FGFR3 0.4%, FGFR4 0.0% n=4, MET 0.4%, NOTCH1 0.0% n=1, NOTCH2 0.2%, NRG1 0.2%, PDGFB 0.0% n=3, PDGFRA 0.1%, PDGFRB 0% n=0, RAF1 0.2%, RET 0.5%, ROS1 0.2%, excluding NTRK positive cases. The incidence of NTRK 1/2/3 fusions was 1.25%, while 3.8% of patients have other fusions included on the Targeted Panel in the absence of an NTRK fusion. Two (2, 0.02%) patients had both an NTRK fusion and an additional fusion covered on one of the other 16 genes in the Targeted NGS fusion panel. Conclusion: Actionable fusions showed a combined prevalence in the clinical setting of 5.1%. This study demonstrates that when fusion testing is performed, four times more patients can benefit from a therapeutic option than when testing for these 16 genes compared to the widespread panel of the current clinicians’ favorite choice of only NTRK fusions. More data and education are needed to change the testing paradigm of treating physicians to test broader sets of fusions when assay performance and financial considerations are equal to increase cancer care access. Citation Format: Chaugiang Duong, Steven Lau-Rivera, Rory Jackson, Pathum Kanagasunderam, Roya Hariri, Nathan Montgomery, Derek Lyle, Fernando Lopez Diaz. A study of the clinical utility of NTRKs only vs. comprehensive gene fusion panel testing from a single assay platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1312.