Pichler, R. and van Creij, N. C. H. and Subiela, J. D. and Cimadamore, A. and Cano-Velasco, J. and Tully, K. H. and Mori, K. and Contieri, R. and Afferi, L. and Mari, A. and Soria, F. and Del Giudice, F. and D'Elia, C. and Mayr, Roman and Mertens, L. S. and Pyrgidis, N. and Moschini, M. and Gallioli, A. (2025) Biological and therapeutic implications of FGFR alterations in urothelial cancer: A systematic review from non-muscle-invasive to metastatic disease. ACTAS UROLOGICAS ESPANOLAS, 49 (5): 501719. ISSN 0210-4806, 1699-7980
Full text not available from this repository. (Request a copy)Abstract
FGFR3 mutations are among the most frequent genomic alterations in urothelial cancer (UC) being mainly associated with the luminal papillary (LumP) subtype. With the establishment of fibroblast growth factor receptor (FGFR) inhibitors, the treatment of UC is now shifting more and more towards personalized medicine. A systematic review using Medline and scientific meeting records was carried out according to the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines to assess the potential role of FGFR inhibitors in combination with additional therapies for the management of UC. Ongoing trials were identified via a systematic search on ClinicalTrials.gov. A total of 11 full-text papers, 10 congress abstracts, and 5 trials on ClinicalTrials.gov were identified. Following the BLC2001 and THOR study, erdafitinib is the only approved FGFR1-4 inhibitor for metastatic UC with susceptible FGFR2/3 alterations following platinum-based chemotherapy. According to the THOR data of cohort 2, erdafitinib should not be recommended in patients who are eligible for and have not received prior immune checkpoint inhibitors (ICIs). One phase 3 trial is currently evaluating the intravesical device system (TAR210) in FGFR-altered intermediate non-muscle invasive bladder cancer (MoonRISe-1). Preclinical evidence suggests that combination-based approaches could be considered to improve the efficacy of FGFR inhibitors in patients with UC. Nine phase 1b/2 trials are focusing on the combination of FGFR inhibitors with ICIs, chemotherapy, or enfortumab vedotin. In metastatic disease, some preliminary analyses have reported promising results from these combinations (e.g. NORSE and FORT-2 trial). However, no phase 3 trial is terminated, so there is currently no level 1 evidence with long-term outcomes to support the combination of FGFR inhibitors with ICIs, chemotherapy, or targeted therapies. A better understanding of the different mechanisms of action to inhibit FGFR signaling pathways, optimal patient selection and treatment approaches is still needed. (c) 2025 The Authors. Published by Elsevier Espana, S.L.U. on behalf of AEU. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR RECEPTOR; BLADDER-CANCER; SINGLE-ARM; CARCINOMA; TRIAL; PEMBROLIZUMAB; MULTICENTER; DOVITINIB; BINDING; TARGET; FGFR; FGFR inhibition; FGFR3 mutation; Bladder Cancer; Urothelial cancer; TAR210 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Urologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Aug 2026 06:51 |
| Last Modified: | 12 Aug 2026 06:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67763 |
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