Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Expert Opin Biol Ther. 2021 Jul;21(7):915-922. doi: 10.1080/14712598.2020.1789096. Epub 2020 Jul 3.
The therapeutic landscape for urothelial carcinoma has changed significantly over the past few years with the addition of immunotherapy to platinum-based chemotherapy. Targeted therapy against FGFR (fibroblast growth factor receptor) is now also approved for the minority of patients with FGFR aberrations. Antibody-drug conjugates (ADCs) are of great interest in urothelial carcinoma, with a recent FDA approval for enfortumab vedotin (EV) and others in development.
This review will provide an overview of treatment of advanced urothelial carcinoma and detail the various ADCs being studied in this disease.
ADCs are an important therapeutic option for urothelial carcinoma. Responses to EV exceeded 40% in heavily pre-treated patients, while the response rate to EV combined with pembrolizumab in a phase 1b trial was ~70% in treatment-naïve patients. EV has already been approved in the United States and we await randomized data to confirm a survival benefit with EV. Meanwhile, studies of other ADCs, including in biomarker-selected populations, are ongoing. ADCs will undoubtedly play an increasing role in the management of urothelial carcinoma and will likely be offered earlier in the disease course, resulting in significant changes to treatment algorithms in urothelial cancer in the coming years.
在过去的几年中,随着免疫疗法加入铂类化疗,尿路上皮癌的治疗格局发生了重大变化。针对 FGFR(成纤维细胞生长因子受体)的靶向治疗现在也被批准用于少数 FGFR 异常的患者。抗体药物偶联物(ADC)在尿路上皮癌中引起了极大的关注,最近 FDA 批准了 enfortumab vedotin(EV),其他药物也在开发中。
本文综述将概述晚期尿路上皮癌的治疗方法,并详细介绍正在该疾病中研究的各种 ADC。
ADC 是尿路上皮癌的重要治疗选择。在经过大量预处理的患者中,EV 的缓解率超过 40%,而在 1b 期试验中,EV 联合 pembrolizumab 的缓解率在初治患者中约为 70%。EV 已在美国获得批准,我们正在等待随机数据来确认 EV 的生存获益。与此同时,其他 ADC 的研究,包括在生物标志物选择人群中的研究,正在进行中。ADC 无疑将在尿路上皮癌的治疗管理中发挥越来越重要的作用,并可能在疾病早期提供治疗,从而在未来几年中对尿路上皮癌的治疗算法产生重大变化。