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[乳腺癌中与抗体药物偶联物相关的治疗相关不良事件]

[Treatment-related adverse events associated with antibody drug conjugate in breast cancer].

作者信息

Collineau Bérénice, Gonçalves Anthony, Bertucci François, de Nonneville Alexandre

机构信息

Department of Medical Oncology, CRCM, Aix-Marseille université, CNRS, Inserm, Institut Paoli-Calmettes, Marseille, France.

Department of Medical Oncology, CRCM, Aix-Marseille université, CNRS, Inserm, Institut Paoli-Calmettes, Marseille, France; Laboratory of Predictive Oncology, Centre de recherche en cancérologie de Marseille, Institut Paoli-Calmettes, Inserm UMR1068, CNRS UMR725, équipe labellisée Ligue nationale contre le cancer, Marseille, France.

出版信息

Bull Cancer. 2024 Jul-Aug;111(7-8):765-781. doi: 10.1016/j.bulcan.2024.04.004. Epub 2024 May 20.

Abstract

Therapeutic options for breast cancer have recently been enriched by new antibody-drug conjugates (ADC), which are now being utilized across all known molecular subtypes. ADCs represent a groundbreaking class of therapies that combine a cytotoxic agent with a monoclonal antibody via a combination molecule (linker). The primary objective is to selectively deliver chemotherapy to cells expressing the target antigen, thereby enhancing the therapeutic index. Trastuzumab-emtansine marked the pioneering use of this approach for HER2-overexpressed breast cancer. More recently, trastuzumab-deruxtecan and sacituzumab-govitecan have demonstrated efficacy in progression-free survival and overall survival in HER2-overexpressed and HER2-low breast cancer for the former, and HER2-non-overexpressed (including HER-low) for the latter. Numerous other ADCs are currently under development in breast cancer. While ADCs were initially designed to widen the therapeutic index and mitigate toxicities, managing ADC-related adverse events in the clinical setting remains a challenge. This review article aims to provide an overview of the toxicity profiles of these drugs already in current clinical practice or under development, drawing from results observed in various studies.

摘要

最近,新型抗体药物偶联物(ADC)丰富了乳腺癌的治疗选择,目前这些药物正应用于所有已知的分子亚型。ADC代表了一类开创性的疗法,它通过一种结合分子(连接子)将细胞毒性药物与单克隆抗体结合。其主要目的是将化疗药物选择性地递送至表达靶抗原的细胞,从而提高治疗指数。曲妥珠单抗-恩美曲妥珠单抗标志着这种方法在HER2过表达乳腺癌中的首次应用。最近,曲妥珠单抗-德曲妥珠单抗和戈沙妥珠单抗在前一种药物用于HER2过表达和HER2低表达乳腺癌、后一种药物用于HER2非过表达(包括HER低表达)乳腺癌的无进展生存期和总生存期方面均显示出疗效。目前在乳腺癌领域还有许多其他ADC正在研发中。虽然ADC最初旨在扩大治疗指数并减轻毒性,但在临床环境中管理与ADC相关的不良事件仍然是一项挑战。这篇综述文章旨在根据各项研究中观察到的结果,概述这些已在临床实践中应用或正在研发的药物的毒性特征。

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