Zhonghua Zhong Liu Za Zhi. 2022 Sep 23;44(9):913-927. doi: 10.3760/cma.j.cn112152-20220521-00360.
As a newly emerged class of anticancer bioagents in the most precise and selectively targeted way, antibody-drug conjugate (ADC) combines the cancer-targeting abilities of monoclonal antibodies with the cytotoxicity potency of payload, delivering highly cytotoxic drug into tumors via 'targeted chemotherapy'. ADC has revolutionized the treatment landscape of human epidermal growth factor receptor 2 positive and triple negative subtypes in breast cancer. Three ADCs have been approved by U. S. Food and Drug Administration with breast cancer indications, including trastuzumab emtansine (T-DM1; also approved in China), trastuzumab deruxtecan (T-DXd, DS-8201) and sacituzumab govitecan (IMMU-132; also approved in China). Antibodies, cytotoxic drug, linker, and conjugation process are implicated in ADC profile, resulting in unique adverse drug reactions and toxicity heterogeneity within ADC class. For example, more attention should be paid to the management of thrombocytopenia, hepatotoxicity, and reductions in left ventricular ejection fraction (LVEF) in patients treated with trastuzumab emtansine; clinical physicians should pay attention to the risk of neutropenia, interstitial lung disease/pneumonitis, and reductions in LVEF when treated with trastuzumab deruxtecan; sacituzumab govitecan most frequently caused neutropenia, anemia and diarrhea requiring close monitor. ADC has generally favorable safety profiles, and dose modifications and/or symptomatic supporting treatment are effective in terms of toxicity management. This consensus aims at providing guidance for clinical oncologists of early detection, regular assessment, timely management and follow-up monitor of ADC-associated adverse reactions/events.
作为一类以最精确和选择性靶向方式新出现的抗癌生物制剂,抗体药物偶联物(ADC)将单克隆抗体的癌症靶向能力与有效载荷的细胞毒性相结合,通过“靶向化疗”将高细胞毒性药物输送到肿瘤中。ADC彻底改变了人类表皮生长因子受体2阳性和三阴性亚型乳腺癌的治疗格局。美国食品药品监督管理局已批准三种用于乳腺癌适应症的ADC,包括曲妥珠单抗恩美曲妥珠单抗(T-DM1;在中国也已获批)、曲妥珠单抗德曲妥珠单抗(T-DXd,DS-8201)和赛托珠单抗戈维汀(IMMU-132;在中国也已获批)。抗体、细胞毒性药物、连接子和偶联过程与ADC的特性有关,导致ADC类药物存在独特的药物不良反应和毒性异质性。例如,接受曲妥珠单抗恩美曲妥珠单抗治疗的患者应更多关注血小板减少症、肝毒性以及左心室射血分数(LVEF)降低的管理;临床医生在使用曲妥珠单抗德曲妥珠单抗治疗时应注意中性粒细胞减少症、间质性肺病/肺炎以及LVEF降低的风险;赛托珠单抗戈维汀最常引起中性粒细胞减少症、贫血和腹泻,需要密切监测。ADC总体上具有良好的安全性,剂量调整和/或对症支持治疗在毒性管理方面是有效的。本共识旨在为临床肿瘤学家在早期发现、定期评估、及时管理和随访监测ADC相关不良反应/事件方面提供指导。