VEGF inhibition in urothelial cancer: the past, present and future.

Purpose: To describe the role of anti-angiogenic agents that have been used as a treatment approach for locally advanced or metastatic urothelial cancers and to propose future directions.

Methods: PubMed/MEDLINE was searched for articles related to VEGF inhibition and locally advanced or metastatic urothelial cancer.

Results: Angiogenesis is a fundamental process for urothelial cancer initiation and progression. First-line therapy for locally advanced or metastatic urothelial cancer includes cisplatin-based chemotherapy combinations; subsequent systemic therapy includes taxanes, nanoparticle albumin-bound (nab) paclitaxel, or pemetrexed. More recently, several anti-PD-L1 and anti-PD-1 antibodies have shown promising activity in the first-line and post-platinum setting; however, immunotherapy remains ineffective in most patients. FGFR inhibitor erdafitinib was recently approved in the third-line setting. Studies on bevacizumab, pazopanib and ramucirumab have shown improved response rates when added to chemotherapy in selected patients, but have not led to overall survival (OS) benefit in randomized controlled studies.

Conclusion: Anti-angiogenic agents have shown promise in recent studies treating locally advanced or metastatic urothelial cancer. However, further work is needed to elucidate ideal treatment combinations in selected patient populations to maximize benefit, with the ultimate goal of being added to the FDA-approved treatment armamentarium for this disease.