TEST:

therascreen® FGFR RGQ RT-PCR Kit

Urine testing identifies additional NMIBC pts who may respond to erdafitinib, which is especially valuable when the parallel tissue sample submitted does not return a result. Findings support urine testing for pt selection in the recently initiated phase 3 study (MoonRISe-1, NCT06319820).

Implementing a urine-based assay expands the molecular testing methods to identify additional patients that may respond to erdafitinib. Results justify further study. Clinical trial information: NCT05316155.

Background: In view of the efficacy of FGFR targeting in early and advanced bladder cancer, as has been shown for erdafitinib in the THOR and NORSE trial, molecular testing of FGFR mutations and fusions will soon become clinical routine worldwide... PCR-based FGFR assessment by Therascreen and UroTyper is highly concordant and enables fast, local FGFR assessment within few hours. FGFR3 mutations are associated with increased TROP2 & NECTIN4 expression indicating potential synergistic options which warrants further exploration as part of molecularly stratified clinical trials.

To receive the drug, alteration testing is required, and only alteration carriers can profit of this new agent. Due to this clinical need of detection and analysis of FGFR, here we describe two distinct and specific analytical methodologies: the SNaPshot analysis of nine FGFR3 point mutations and the QIAGEN therascreen FGFR RGQ RT-PCR Kit, the FDA-approved companion diagnostic kit.

Despite significant breakthroughs in targeted medicines (i.e., Erdafitinib, FGFR2/3 kinase inhibitor) and clinical care over the past decade, non-invasive molecular testing remains an unmet clinical need for the treatment of bladder cancer patients... High concordance between FGFR alterations detected with an FDA approved tissue CDx and urine cfDNA NGS assay demonstrates that the PredicineCARE urine cfDNA NGS assay may represent a novel, accurate, and non-invasive clinical application for molecular diagnostic testing to identify biomarkers in bladder cancer.

"Qiagen Korea said on Friday it received domestic approval from the Ministry of Food and Drug Safety for Korea's first companion diagnostic (CDx) that can detect FGFR 3 (fibroblast growth factor receptor 3) gene mutations in urothelial cancer patients...With the approval of the therascreen FGFR kit, patients with urothelial cancer can more accurately and safely test for the FGFR 3 gene and receive more appropriate and effective treatment according to their specific genetic mutations..."

Variant histology was appreciated in 76% of FGFR mutated cases, with the micropapillary pattern being the most prevalent (n=12 | 32%). The FGFR pathway is classically associated with low-grade papillary tumors, which, through additional mutations, can cause invasive, high-grade disease. It is speculated that the initial papillary architecture present in FGFR mutated lesions may be preserved, manifesting as the micropapillary pattern appreciated in some invasive lesions.

Table: 145P FGFR status versus PD-L1 expression in mUC Conclusions This retrospective study showed high unmet needs under SoC in mUC in Taiwan, irrespective of FGFR status. The negative association between FGFR status and PD-L1 expression might be considered when deciding personalized treatment based on biomarker profiles.

Conclusions This retrospective study showed high unmet needs under SoC in mUC in Taiwan, irrespective of FGFR status. The negative association between FGFR status and PD-L1 expression might be considered when deciding personalized treatment based on biomarker profiles.

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. >

Despite a better response to first line treatment, overall FGFR GA showed to be an independent risk factor in mUC. Thus, this determination should be included in new prognostic models. Univariable and multivariable analysis for overall survival in the first line treatment setting for mUC.

Extraction of exosomal RNA from urine followed by highly sensitive dPCR mutation testing is feasible with good concordance to matched tissue testing. Urine testing might evolve as alternative approach for FGFR3 screening in a non invasive fashion without the need of transurethral biopsy. Interestingly, mRNA assessment of exosomal RNA from urine before TURB correlated with clinical parameters such as WHO Grade 1973 with ERBB2 mRNA being associated with high grade tumors and FGFR3 mRNA being associated with low grade tumors, which is in line with previous tissue tsting results.

Filtering urine for cells and subsequent DNA extraction followed by PCR detection results in highly sensitive mutation testing being feasible with good concordance to matched tissue testing. Prospective testing validated the diagnostic accuracy of the Uromonitor FGFR test in a real world setting.