Karmanos Cancer Institute, Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA.
Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nat Rev Urol. 2021 Feb;18(2):93-103. doi: 10.1038/s41585-020-00394-5. Epub 2020 Nov 25.
Bladder cancer is the tenth most common cancer type worldwide. Urothelial carcinoma is the most common type of bladder cancer and accounts for 90% of bladder cancer cases in the USA and Europe. Novel approaches are needed to improve patient outcomes. Nectin-4 is a tumour-associated antigen found on the surface of most urothelial carcinoma cells. In the antibody-drug conjugate enfortumab vedotin, human anti-nectin-4 antibody is linked to the cytotoxic microtubule-disrupting agent monomethyl auristatin E. In ongoing phase I, II and III clinical trials, enfortumab vedotin has been evaluated as a monotherapy and in combination with a checkpoint inhibitor and/or chemotherapy in locally advanced and metastatic urothelial carcinoma. Encouraging data from the phase II study resulted in the FDA granting accelerated approval for enfortumab vedotin in December 2019 for patients with locally advanced or metastatic urothelial carcinoma who were previously treated with platinum and a checkpoint inhibitor therapy. Moreover, data from a phase I study led to the FDA granting breakthrough therapy designation to enfortumab vedotin combined with pembrolizumab as a first-line treatment in February 2020 for cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma. Results of ongoing and future combination studies of enfortumab vedotin with immunotherapy and other novel agents are eagerly awaited.
膀胱癌是全球第十大常见癌症类型。尿路上皮癌是最常见的膀胱癌类型，占美国和欧洲膀胱癌病例的 90%。需要新的方法来改善患者的预后。Nectin-4 是一种肿瘤相关抗原，存在于大多数尿路上皮癌细胞表面。在抗体药物偶联物 enfortumab vedotin 中，人抗 nectin-4 抗体与细胞毒性微管破坏剂单甲基奥瑞他汀 E 相连。在正在进行的 I 期、II 期和 III 期临床试验中，enfortumab vedotin 已被评估为单药治疗以及与检查点抑制剂和/或化疗联合用于局部晚期和转移性尿路上皮癌。来自 II 期研究的令人鼓舞的数据导致 FDA 在 2019 年 12 月加速批准 enfortumab vedotin 用于先前接受铂类和检查点抑制剂治疗的局部晚期或转移性尿路上皮癌患者。此外，来自 I 期研究的数据导致 FDA 在 2020 年 2 月授予 enfortumab vedotin 联合 pembrolizumab 突破性治疗指定，用于顺铂不耐受的局部晚期或转移性尿路上皮癌患者的一线治疗。人们急切地等待着正在进行和未来的 enfortumab vedotin 与免疫疗法和其他新型药物联合研究的结果。
