Bladder cancer is common and challenging to treat. Thorough assessment of the molecular biology and immunology background has pinpointed potential biomarkers, “drivers” and promising therapeutic targets. The advent of immune checkpoint inhibitors (ICI) has heralded a new era after approximately two decades of a “stagnant landscape”. As single agents in patients with advanced urothelial carcinoma, ICI can induce rapid and durable responses, with a very small proportion of patients achieving long term remission. However, most patients do not achieve response, while a proportion may have immune-related adverse events. Therefore, there is an urgent need for additional therapies that can raise the bar, improve quality of life, and further prolong life in this tumor.
At the era of next generation sequencing and the report of ‘The Cancer Genome Atlas Project”, there has been renewed interest in the field of targeted therapies, which have encountered significant challenges due to tumor heterogeneity, genomic instability and clonal evolution. The recent development of new agents and companion diagnostic assays signaled a new age of experimental therapeutics in urothelial carcinoma. As a result, the first targeted therapy for this cancer was approved by the FDA on April 12, 2019. Erdafitinib, an orally available pan-FGFR inhibitor, received accelerated approval based on impressive overall response rate and acceptable toxicity profile noted in a phase II trial in patients with metastatic bladder cancer harboring Fibroblast Growth Factor Receptor 2/3 genomic alterations noted on a companion diagnostic assay (RT-PCR by Qiagen).
There is a variety of additional compounds also being evaluated, such inhibitors of receptors and signaling pathways (e.g., Fibroblast Growth Factor Receptor, Human Epidermal growth factor Receptor, Phosphatidylinositol 3-kinase/AKT/mTOR pathway), angiogenesis (e.g. Vascular Endothelial Growth Factor and receptors), Poly (ADP-Ribose) Polymerase inhibitors, cytotoxic agents (e.g. chemotherapy, antibody drug conjugates), immuno-oncology drugs, epigenetic modulators, etc. Enfortumab-vedotin (antibody drug conjugate) has breakthrough designation by the FDA, but is not approved yet, as of May 19, 2019; results from the phase II trial has been presented at the 2019 Annual ASCO Meeting. Novel combinations and optimal therapy sequencing are being tested in promising clinical trials. Prospective validation of predictive (and prognostic) biomarkers with clinical utility, biomarker-based patient selection, and novel clinical trial designs will play major roles in how the field will move forward.
We look forward to discussing updated data in more detail at our newly launched Bladder Cancer Center of Excellence!
- To review standard of care, evidence-based patterns, and key clinical trials in the continuum of bladder cancer care
- To interview key opinion leaders and experts for their perspectives and vision
- To identify key current clinical questions and provide relevant suggestions and thoughts
- To generate an interactive dialogue about high priorities and practice changing ideas