Abstract 4010: Analytical concordance of 3 independent diagnostic assays for the detection of FGFR alterations in urothelial carcinoma tumor tissue

Abstract

Abstract Background: The Qiagen therascreen® companion diagnostic is FDA approved to aid identifying patients with urothelial carcinoma who harbor susceptible fibroblast growth factor receptor (FGFR) gene alterations and are therefore eligible for treatment with erdafitinib, an FGFR inhibitor. We examined analytical concordance between the Qiagen assay against 2 next-generation sequencing (NGS) platforms used to identify molecular targets for tailored treatment, including FGFR alterations. Methods: Formalin-fixed paraffin-embedded tumor tissue samples (N = 54: muscle-invasive bladder cancer [n = 18], non-muscle-invasive bladder cancer [n = 23], cholangiocarcinoma [n = 12], non-small-cell lung cancer [n = 1]) were obtained commercially. FGFR alterations were detected using the Qiagen therascreen FGFR RGQ RT-PCR Kit and tested for concordance vs NGS platforms from Thermo Fisher Scientific (Oncomine Comprehensive™ assay) and Illumina (TruSight™ Oncology 500 [TSO500]). Concordance assessment of positive, negative, and overall agreement was done. Results: 54 samples yielded valid results using the Qiagen assay. 51 met quality control metrics with the Thermo Fisher assay, and 47 with the Illumina assay. FGFR alterations were found in 17 samples, including 16 with single nucleotide variants (SNVs): R248C (n = 1), S249C (n = 7), and Y373C (n = 8), 1 with an FGFR3:TACC3 fusion and 1 with both FGFR3:TACC3 fusion and S249C mutation. Qualitative positive agreement (100%), negative agreement (100%), and overall agreement (100%) between the Thermo Fisher NGS assay and the Illumina NGS assay vs the Qiagen assay for SNVs was observed (Table). 2 fusions detected as positive by the Qiagen assay were not identified as the TACC3v1 fusion by NGS assays. Conclusions: There was a high level of analytical concordance in detection of FGFR alterations indicated for erdafitinib between the Qiagen companion diagnostic assay and 2 commercially available NGS platforms. Table. Concordance in detection of FGFR alterations Qiagen therascreen RT-PCR Positive Negative NGS Thermo Fisher Oncomine Dx Positive 17/17 (100%); 95% CI, 86.3%-100% 0/34 (0) Negative 0/17 (0) 34/34 (100%); 95% CI, 92.6%-100% Overall 51/51 (100%); 95% CI, 95.0%-100% NGS Illumina TSO500 Positive 17/17 (100%); 95% CI, 86.3%-100% 0/30 (0) Negative 0/17 (0) 30/30 (100%); 95% CI, 91.7%-100% Overall 47/47 (100%); 95% CI, 94.6%-100% Citation Format: Christopher Major, Songbai Wang. Analytical concordance of 3 independent diagnostic assays for the detection of FGFR alterations in urothelial carcinoma tumor tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4010.