Enfortumab Vedotin in urothelial cancer. (December 2020)

• Record Type: Journal Article
• Authors: Alt, Marie; Stecca, Carlos; Tobin, Swanee; Jiang, Di Maria; Sridhar, Srikala S.
• Is Part Of: Therapeutic advances in urology. Volume 12(2020)
• Publication Date: 2020-12
• Subjects: Antibody-drug conjugates -- Metastatic Urothelial Carcinoma -- Enfortumab Vedotin; Urology -- Periodicals; Urologic Diseases -- therapy -- Periodicals; Genital Diseases, Male -- therapy -- Periodicals; Urologie -- Périodiques; 616.6005
• DOI: 10.1177/1756287220980192
• Languages: English
• ISSNs: 1756-2872

Abstract

The treatment landscape for metastatic urothelial cancer (mUC) beyond first-line platinum-based chemotherapy has changed significantly over the last 5 years with the recent approvals of the immune checkpoint inhibitors (ICIs), fibroblast growth factor receptor (FGFR) inhibitors and most recently Enfortumab Vedotin (EV). EV is a novel antibody–drug conjugate (ADC), that delivers monomethyl auristatin E (MMAE), a microtubule-disrupting agent, inside cells harboring the cell surface nectin-4 receptor. In mUC, EV has shown encouraging response rates and received accelerated approval from the Food and Drug Administration (FDA) in December 2019 in the post-platinum and ICI setting. EV is generally well tolerated, with the main toxicities being neuropathy, skin rash, alopecia and fatigue. Notably EV can also be administered to patients with renal dysfunction, which is commonly a concern in this patient population. EV is now being tested in combination strategies and in earlier disease settings in urothelial cancers. In this review, we will discuss its mechanism of action, clinical trials leading to FDA approval as well as ongoing trials and future directions.