Fibroblast Growth Factor Receptor Alteration Testing for >3600 Patients with Locally Advanced/Metastatic Urothelial Cancer and Non-muscle-invasive Bladder Cancer: An Analysis of the Global ANNAR Biomarker Study.

Abstract

Background and objective: Successful fibroblast growth factor receptor alterations (FGFRalt) testing is essential for identifying patients eligible for erdafitinib. This analysis of the global ANNAR biomarker study assessed the proportion of valid fibroblast growth factor receptor (FGFR) test results, reasons for test failure, and proportion of FGFRalt in locally advanced/metastatic urothelial cancer (mUC) and non-muscle-invasive bladder cancer (NMIBC).

Methods: Archival tumor tissue was tested using the QIAGEN therascreen FGFR real-time polymerase chain reaction kit, an approved companion diagnostic for erdafitinib.

Key findings and limitations: A total of 2706 mUC and 962 NMIBC samples were tested. The proportion of valid test results was significantly different between mUC and NMIBC (86% and 66%, respectively; p < 0.001), which declined with older archival sample age for both mUC (<1 yr 89% and ≥3 yr 77%; p < 0.001) and NMIBC (<1 yr 72% and ≥3 yr 43%; p < 0.001). For mUC, the proportion of valid test results was higher for the primary tumor than for metastatic samples (92% and 55%, respectively; p < 0.001) but similar between upper and lower tract disease (87% and 86%, respectively; p = 0.7). Common reasons for test failure were low tumor content and insufficient RNA. FGFRalt were found in 19% of mUC (83% mutations; 15% fusions) and 53% of NMIBC (92% mutations; 6.3% fusions) samples. Limitations include the lack of data on sample collection method.

Conclusions and clinical implications: This is the first and largest report on factors affecting FGFR test results. To ensure valid FGFR test results, adequate tumor sample amount, RNA quality, short archival sample age, and primary tumor samples are important factors.