Koster Kira-Lee, Huober Jens, Joerger Markus
Medical Oncology and Hematology, Cantonal Hospital, CH-9000 St. Gallen, Switzerland.
Breast Center, Cantonal Hospital, CH-9000 St. Gallen, Switzerland.
Explor Target Antitumor Ther. 2022;3(1):27-36. doi: 10.37349/etat.2022.00069. Epub 2022 Feb 24.
Antibody-drug conjugates (ADCs) have changed the treatment of breast cancer (BC) in more recent years. BC is a heterogenous group of malignancies with a broad range of histopathological characteristics. ADCs represent a class of therapeutics that combines an antigen-specific antibody backbone bound to a potent cytotoxic agent (the payload), via a linker, contributing to an improved therapeutic index. Currently, three ADCs received approval by the US Food and Drug Administration (FDA) and are in routine clinical use in different treatment settings; many more ADCs are in earlier and later stages of development, and their future approval will improve treatment options for patients with advanced but potentially also early-stage BC over time. Just recently, the results of three phase 3 trials (ASCENT, TULIP, and DESTINY-Breast03) evaluating sacituzumab govitecan (SG), trastuzumab duocarmazine, and trastuzumab deruxtecan (T-DXd) in different treatment settings were presented and showed promising results. This overview focuses on the newer ADCs, including T-DXd and SG, their pharmacology, mechanisms of action, and relevant studies. In addition, the latest results from trials investigating some newer ADCs, in further stages of development are presented.
近年来,抗体药物偶联物(ADC)改变了乳腺癌(BC)的治疗方式。BC是一组具有广泛组织病理学特征的异质性恶性肿瘤。ADC是一类治疗药物,它通过连接子将抗原特异性抗体骨架与强效细胞毒性药物(有效载荷)结合,从而提高治疗指数。目前,有三种ADC已获得美国食品药品监督管理局(FDA)的批准,并在不同的治疗环境中常规临床使用;还有更多的ADC正处于早期和后期开发阶段,随着时间的推移,它们未来的获批将改善晚期乃至早期BC患者的治疗选择。就在最近,三项评估赛托珠单抗戈维汀(SG)、曲妥珠单抗多卡莫嗪和曲妥珠单抗德鲁替康(T-DXd)在不同治疗环境中的3期试验(ASCENT、TULIP和DESTINY-Breast03)结果公布,显示出了有前景的结果。本综述重点关注包括T-DXd和SG在内的新型ADC、它们的药理学、作用机制及相关研究。此外,还介绍了一些处于进一步开发阶段的新型ADC试验的最新结果。