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Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer.在转移性三阴性乳腺癌患者中 sacituzumab govitecan 与化疗对比的 III 期 ASCENT 研究中的生物标志物分析。
Ann Oncol. 2021 Sep;32(9):1148-1156. doi: 10.1016/j.annonc.2021.06.002. Epub 2021 Jun 8.
2
Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer.Sacituzumab Govitecan 治疗转移性三阴性乳腺癌。
N Engl J Med. 2021 Apr 22;384(16):1529-1541. doi: 10.1056/NEJMoa2028485.
3
Clinical Development of New Antibody-Drug Conjugates in Breast Cancer: To Infinity and Beyond.新型抗体药物偶联物在乳腺癌中的临床开发:走向无限与超越。
BioDrugs. 2021 Mar;35(2):159-174. doi: 10.1007/s40259-021-00472-z. Epub 2021 Mar 5.
4
Sacituzumab govitecan in previously treated hormone receptor-positive/HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial.在既往治疗的激素受体阳性/HER2 阴性转移性乳腺癌中应用 sacituzumab govitecan:一项 I/II 期、单臂、篮子试验的最终结果。
Ann Oncol. 2020 Dec;31(12):1709-1718. doi: 10.1016/j.annonc.2020.09.004. Epub 2020 Sep 15.
5
Antibody-Drug Conjugates: The Last Decade.抗体药物偶联物:过去十年
Pharmaceuticals (Basel). 2020 Sep 14;13(9):245. doi: 10.3390/ph13090245.
6
Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low-Expressing Advanced Breast Cancer: Results From a Phase Ib Study.曲妥珠单抗-德鲁替康在 HER2 低表达晚期乳腺癌患者中的抗肿瘤活性和安全性:来自一项 Ib 期研究的结果。
J Clin Oncol. 2020 Jun 10;38(17):1887-1896. doi: 10.1200/JCO.19.02318. Epub 2020 Feb 14.
7
Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer.恩美曲妥珠单抗治疗既往 HER2 阳性乳腺癌。
N Engl J Med. 2020 Feb 13;382(7):610-621. doi: 10.1056/NEJMoa1914510. Epub 2019 Dec 11.
8
Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study.曲妥珠单抗 DM1 治疗局部晚期和转移性实体瘤及 HER2 阳性乳腺癌:一项 1 期剂量递增和扩展研究。
Lancet Oncol. 2019 Aug;20(8):1124-1135. doi: 10.1016/S1470-2045(19)30328-6. Epub 2019 Jun 27.
9
Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study.曲妥珠单抗-德鲁替康(DS-8201a)治疗既往接受过曲妥珠单抗-美坦新偶联物治疗的晚期 HER2 阳性乳腺癌患者:一项剂量扩展、I 期研究。
Lancet Oncol. 2019 Jun;20(6):816-826. doi: 10.1016/S1470-2045(19)30097-X. Epub 2019 Apr 29.
10
Antibody-Drug Conjugate-Based Therapeutics: State of the Science.抗体药物偶联物治疗药物:科学现状。
J Natl Cancer Inst. 2019 Jun 1;111(6):538-549. doi: 10.1093/jnci/djz035.

乳腺癌中的新型抗体药物偶联物(ADC)——近期获批及处于后期开发阶段的ADC概述

New antibody-drug conjugates (ADCs) in breast cancer-an overview of ADCs recently approved and in later stages of development.

作者信息

Koster Kira-Lee, Huober Jens, Joerger Markus

机构信息

Medical Oncology and Hematology, Cantonal Hospital, CH-9000 St. Gallen, Switzerland.

Breast Center, Cantonal Hospital, CH-9000 St. Gallen, Switzerland.

出版信息

Explor Target Antitumor Ther. 2022;3(1):27-36. doi: 10.37349/etat.2022.00069. Epub 2022 Feb 24.

DOI:10.37349/etat.2022.00069
PMID:36046357
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9400777/
Abstract

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.

摘要

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。