McGuinness Julia E, Kalinsky Kevin
Department of Medicine, Division of Hematology and Oncology, Columbia University Irving Medical Center, New York, NY, USA.
Department of Medicine, Division of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA, USA.
Expert Opin Biol Ther. 2021 Jul;21(7):903-913. doi: 10.1080/14712598.2021.1840547. Epub 2020 Dec 27.
Metastatic triple-negative breast cancers (mTNBC) are characterized by aggressive behavior and worse clinical outcomes than other breast cancer subtypes, as well as poor response to cytotoxic chemotherapies. The use of antibody-drug conjugates (ADCs) has been investigated as a potential treatment strategy, particularly in heavily pretreated disease.
This article reviews the preclinical and clinical data supporting the use of the ADCs sacituzumab govitecan (SG), ladiratuzumab vedotin (LV), and trastuzumab deruxtecan (T-DXd) in mTNBC, and highlights ongoing clinical trials and future clinical applications.
SG, LV, and T-DXd have demonstrated their potential to meaningfully improve clinical outcomes in patients with pretreated mTNBC, as demonstrated by notable response rates in phase I/II and, for SG, phase III clinical trials. Investigation of their use in combination with other agents, including PARP inhibitors and checkpoint inhibitors, is ongoing in the metastatic setting, and their application in early-stage TNBCs are under investigation. ADCs are therefore expected to redefine treatment paradigms in TNBC.
转移性三阴性乳腺癌（mTNBC）具有侵袭性生物学行为，与其他乳腺癌亚型相比临床结局更差，对细胞毒性化疗的反应也较差。抗体药物偶联物（ADC）已作为一种潜在的治疗策略进行研究，尤其是在经过大量预处理的疾病中。
本文综述了支持在mTNBC中使用ADC药物赛托珠单抗戈维汀（SG）、拉地珠单抗维莫非汀（LV）和曲妥珠单抗德鲁昔康（T-DXd）的临床前和临床数据，并重点介绍了正在进行的临床试验和未来的临床应用。
SG、LV和T-DXd已显示出有潜力显著改善预处理mTNBC患者的临床结局，I/II期以及SG的III期临床试验中的显著缓解率证明了这一点。在转移性疾病中，正在研究它们与其他药物（包括PARP抑制剂和检查点抑制剂）联合使用的情况，并且它们在早期TNBC中的应用也在研究中。因此，ADC有望重新定义TNBC的治疗模式。
