Ruder Samuel, Martinez Juana, Palmer Jessica, Arham Abdul Baseet, Tagawa Scott T
Department of Medicine, Division of Hematology and Oncology, New York Presbyterian Weill Cornell Medical Center.
Department of Medicine, Icahn School of Medicine at Mount Sinai Hospital, New York, New York, USA.
Curr Opin Urol. 2025 May 1;35(3):292-300. doi: 10.1097/MOU.0000000000001263. Epub 2025 Jan 22.
Antibody-drug conjugates (ADCs) are quickly becoming frontline standard of care in many tumor types, including urothelial carcinoma. This review summarizes recent clinical investigations into the use of ADCs targeting nectin-4, trophoblast cell surface antigen-2 (Trop-2), human epidermal growth factor receptor 2 (HER-2), and other antigens in urothelial carcinoma.
This review covers efficacy and toxicity data of ADCs alone and in combination with immunotherapy; mechanisms of resistance; and preclinical studies that provide biological basis for clinical approaches.
Enfortumab vedotin and sacituzumab govitecan can be used in an unselected group of patients with urothelial carcinoma whereas HER-2 ADCs have only been administered in those with high expression or amplification. Most are being studied in combination with immune checkpoint inhibitors. Data supports use of enfortumab vedotin in combination with pembrolizumab as first-line therapy in metastatic/unresectable locally advanced urothelial carcinoma. Sacituzumab govitecan may be used as later-line option in these patients. HER-2 therapy is still under investigation but has many recent promising results.
抗体药物偶联物（ADC）正迅速成为包括尿路上皮癌在内的多种肿瘤类型的一线标准治疗方案。本综述总结了近期针对尿路上皮癌中靶向Nectin-4、滋养层细胞表面抗原2（Trop-2）、人表皮生长因子受体2（HER-2）及其他抗原的ADC的临床研究。
本综述涵盖了ADC单独使用及与免疫疗法联合使用的疗效和毒性数据；耐药机制；以及为临床治疗方法提供生物学基础的临床前研究。
恩杂鲁胺和戈沙妥珠单抗可用于未筛选的尿路上皮癌患者群体，而HER-2 ADC仅用于高表达或扩增的患者。大多数正在研究与免疫检查点抑制剂联合使用。数据支持恩杂鲁胺与帕博利珠单抗联合用于转移性/不可切除的局部晚期尿路上皮癌的一线治疗。戈沙妥珠单抗可作为这些患者的后线治疗选择。HER-2治疗仍在研究中，但近期有许多有前景的结果。
