Erdafitinib in the Evolving Urothelial Carcinoma Landscape

In this discussion, Thomas Flaig, MD, vice chancellor of research at the University of Colorado Anschutz, addressed the shifting treatment paradigm for advanced urothelial carcinoma and the strategic role of erdafitinib, an FGFR inhibitor. He notes that the traditional backbone of platinum-based chemotherapy has been “shuffled” by the emergence of frontline regimens such as enfortumab vedotin plus pembrolizumab, which are now preferred by the NCCN. Consequently, the clinical question has shifted to determining optimal sequencing after frontline therapy.

According to Dr Flaig, post-frontline options generally fall into 2 categories: traditional chemotherapy, such as cisplatin plus gemcitabine or dose-dense methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin, or biomarker-driven therapy. For patients with FGFR3 alterations, erdafitinib serves as a viable option in the second-line setting or after chemotherapy. He emphasizes that guideline recommendations position it as an option alongside other treatments, making the choice an individualized clinical decision.

Regarding adverse event management, Dr Flaig highlights two critical toxicities associated with erdafitinib. First, hyperphosphatemia is a unique on-target side effect that requires careful monitoring. While dietary modifications are sometimes attempted, he notes that dose reduction is often necessary to manage phosphate levels effectively. Second, he stresses the importance of ophthalmologic monitoring, recommending close, monthly assessments early in treatment, in collaboration with eye care colleagues, to address potential ocular changes.