Clinical Evidence and Selecting Patients for Treatment with Erdafitinib in Advanced Urothelial Carcinoma

Nicolas Sayegh, Nishita Tripathi, Neeraj Agarwal, Umang Swami Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USACorrespondence: Umang Swami, Division of Oncology, Huntsman Cancer Institute, University of Utah (NCI-CCC), 2000 Circle of Hope Drive Research North Bldg Suite No. 2121, Salt Lake City, UT, 84112, USA, Tel +1 801 587 4697, Email umang.swami@hci.utah.eduAbstract: Erdafitinib received accelerated approval on April 12, 2019, for patients with metastatic or locally advanced urothelial carcinoma with susceptible fibroblast growth factor receptor (FGFR) 3 or FGFR2 genetic alterations and who have progressed during or following at least one platinum-based chemotherapy. It thus became the first-ever targeted therapy to receive accelerated FDA approval for metastatic bladder cancer. In the BLC2001 trial, erdafitinib demonstrated an overall response rate of 40% in patients with urothelial carcinoma. Common adverse events include hyperphosphatemia and retinopathy and require regular monitoring. While the increase in serum phosphate levels has been determined to be a pharmacodynamic marker of response, further interrogation of other clinical, genomic, and transcriptomic biomarkers is warranted. Results of the ongoing Phase III trial, THOR, which is comparing erdafitinib to the standard of care (chemotherapy or immunotherapy), are expected to confer full approval. Establishing guidelines for optimal erdafitinib sequencing with immunotherapy and other approved targeted therapies (enfortumab vedotin and sacituzumab govitecan) remains an unmet need.Keywords: advanced urothelial carcinoma, erdafitinib, fibroblast growth factor receptor, targeted therapy, patient selection