Targeted therapies for advanced bladder cancer: new strategies with FGFR inhibitors
Chiara Casadei1, Nazli Dizman2, Giuseppe Schepisi1
1Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Abstract:
Inhibitors of fibroblast growth factor receptor (FGFR) represent an outstanding treatment approach for selected patients with urothelial cancer (UC). These agents are changing the clinical approach to a subgroup of UC, the luminal-papillary subtype, characterized by FGFR mutations, fusions, or amplification. In this review, we provide an overview of the results of recent clinical trials on FGFR tyrosine kinase inhibitors (TKIs) currently in clinical development for the treatment of UC: erdafitinib, rogaratinib, infigratinib, and the monoclonal antibody vofatamab. The Food and Drug Administration recently granted accelerated approval to erdafitinib for patients with advanced UC with alterations of FGFR2 or FGFR3 after progression on platinum-based chemotherapy. We also look at future therapeutic options of combination regimens with immune-checkpoint inhibitors as strategies for improving the antitumor effects of this class of drug, and for preventing or delaying the development of resistance.
Insights
Fibroblast growth factor receptor (FGFR) inhibitors offer a new treatment for urothelial cancer (UC) with specific genetic alterations. These targeted therapies, including erdafitinib, are transforming care for advanced UC patients.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Urothelial cancer (UC) treatment is evolving with targeted therapies.
- Specific subtypes of UC, like the luminal-papillary subtype, harbor alterations in fibroblast growth factor receptor (FGFR).
- FGFR alterations (mutations, fusions, amplification) are key drivers in a subset of UC.
Purpose of the Study:
- To review recent clinical trials of FGFR tyrosine kinase inhibitors (TKIs) for urothelial cancer.
- To discuss the current landscape and future directions for FGFR-targeted therapies in UC.
- To highlight the potential of combination strategies involving FGFR inhibitors.
Main Methods:
- Review of clinical trial data for FGFR inhibitors in urothelial cancer.
- Analysis of recent FDA approvals and ongoing clinical development.
- Exploration of combination regimens with immune-checkpoint inhibitors.
Main Results:
- FGFR inhibitors are demonstrating significant clinical activity in selected UC patients.
- Erdafitinib received accelerated FDA approval for advanced UC with FGFR2/FGFR3 alterations post-chemotherapy.
- Several FGFR TKIs (erdafitinib, rogaratinib, infigratinib) and a monoclonal antibody (vofatamab) are in clinical development.
Conclusions:
- FGFR inhibitors represent a promising therapeutic class for specific urothelial cancer subtypes.
- Targeted therapy is shifting the treatment paradigm for FGFR-altered UC.
- Combination therapies may enhance efficacy and overcome resistance to FGFR inhibitors.
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