Optimizing management of advanced urothelial carcinoma: A review of emerging therapies and biomarker-driven patient selection

Abstract

Introduction: Advanced urothelial carcinoma has been challenging to treat due to limited treatment options, poor response rates, and poor long-term survival. New treatment options hold the promise of improved outcomes for these patients. Methods: A multidisciplinary working group drafted a management algorithm for advanced urothelial carcinoma using “consensus development conference” methodology. A targeted literature search identified new and emerging treatments for inclusion in the management algorithm. Published clinical data were considered during the algorithm development process, as well as the risks and benefits of the treatment options. Biomarkers to guide patient selection in clinical trials for new treatments were incorporated into the algorithm. Results: The advanced urothelial carcinoma management algorithm includes newly approved first-line anti- programmed death receptor-1 (PD1)/ programmed death-ligand 1 (PD-L1) therapies, a newly approved anti- fibroblast growth factor receptors (FGFR) therapy, and an emerging anti-Nectin 4 therapy, which have had encouraging results in phase 2 trials for secondline and third-line therapy, respectively. This algorithm also incorporates suggestions for biomarker testing of PD-L1 expression and FGFR gene alterations. Conclusions: Newly approved and emerging therapies are starting to cover an unmet need for more treatment options, better response rates, and improved overall survival in advanced urothelial carcinoma. The management algorithm provides guidance on how to incorporate these new options, and their associated biomarkers, into clinical practice.