Abstract 6431: First NGS-based companion diagnostic to aid in the selection of targeted therapy for anaplastic thyroid cancer patients with BRAF V600E mutations
Authors: Clark Thomas , Nater Tristan , Maxfield Jessica , Peterson Justin , Hotchkiss Kristina , Russo Corey , Roth Anne Marie Velasco 
Published: March 2024

Abstract
Introduction: While anaplastic thyroid cancer (ATC) is rare, it is the most aggressive form of thyroid cancer. All ATCs are considered stage IV at diagnosis and response rates to standard systemic therapies are poor with dismal long-term outcomes. As such, molecular profiling of ATCs has increasingly been used to identify therapeutic targets that may inform individualized therapy. Current clinical guidelines recommend molecular profiling, especially BRAF V600E mutation assessment, be performed at the time of ATC diagnosis to inform decisions related to the use of targeted therapies. On September 29, 2023, the FDA granted companion diagnostic approval to the Oncomine™ Dx Target Test (ODxT Test) as an aid in the selection of patients with BRAF V600E-mutated ATC who may be eligible for treatment with dabrafenib in combination with trametinib. Here we report the assay performance data which supports the clinical benefit of the ODxT Test as an aid in the selection of targeted therapy for ATC patients with BRAF V600E mutations.
Methods: The ODxT Test is a targeted next-generation sequencing (NGS) in vitro diagnostic assay used to detect somatic changes in human DNA and RNA isolated from FFPE tissue samples. To validate the clinical benefit of the ODxT Test for the selection of ATC patients with BRAF V600E mutations, a retrospective clinical concordance study was performed on 35 patients enrolled in the ATC cohort of the ROAR trial, a phase II study of dabrafenib in combination with trametinib in subjects with rare cancers with BRAF V600E mutations. The study evaluated the overall percent agreement (OPA), positive percent agreement (PPA), and negative percent agreement (NPA) for the detection of BRAF V600E mutations between the ROAR trial central confirmatory assay, bioMerieux THxID™ BRAF test (THxID), and the ODxT Test. Due to the small number of BRAF V600E-mutated ATC patients enrolled in the ROAR trial, 167 commercially-obtained thyroid cancer specimens were also included in the concordance analysis.
Results: Of the 202 specimens included in the study with a valid ThxID result, 199 had sufficient material for testing with the ODxT Test and were included in the clinical concordance analysis. The point estimates of PPA, NPA and OPA were 99.0%, 100%, and 99.4%, respectively, when excluding ODxT Test invalid results and the lower bounds of the 95% Wilson Score confidence intervals for PPA, NPA, and OPA were 94.4%, 93.7%, and 96.4% respectively.
Conclusion: The ODxT Test was shown to be effective in identifying BRAF V600E mutations in ATC patients through a clinical concordance study using specimens from patients enrolled in the ROAR trial and commercially-sourced samples. The results support the expanded indication to the ODxT Test and marks the first FDA-approved NGS-based companion diagnostic for patients with BRAF V600E-mutated ATC.
Citation Format: Thomas Clark, Tristan Nater, Jessica Maxfield, Justin Peterson, Kristina Hotchkiss, Corey Russo, Anne Marie Velasco Roth. First NGS-based companion diagnostic to aid in the selection of targeted therapy for anaplastic thyroid cancer patients with BRAF V600E mutations [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 6431.