Tarantino Paolo, Morganti Stefania, Uliano Jacopo, Giugliano Federica, Crimini Edoardo, Curigliano Giuseppe
Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS , Milan, Italy.
Department of Oncology and Hematology, University of Milan , Milan, Italy.
Expert Opin Biol Ther. 2021 Feb;21(2):127-133. doi: 10.1080/14712598.2021.1856812. Epub 2020 Dec 14.
No specific standard treatment is currently recommended for HER2-positive advanced breast cancer (BC) patients progressing to dual HER2 blockade and to trastuzumab emtansine (TDM-1). However, several novel anti-HER2 agents are emerging and rapidly revolutionizing this setting. Among these, the FC-engineered monoclonal antibody margetuximab has recently demonstrated to slightly improve progression-free survival (PFS) compared with trastuzumab, when combined with chemotherapy for pretreated HER2-positive advanced BC.
The present review article recapitulates the clinical development of margetuximab, critically discussing its implications in the current landscape of BC treatment algorithms.
The clinical role of Margetuximab can only be interpreted in view of the rapidly evolving treatment landscape for pretreated HER2-positive advanced BC. Indeed, the recently approved anti-HER2 agents tucatinib and trastuzumab deruxtecan currently represent appealing options for the post-TDM1 setting, while margetuximab may have a role after progression to the abovementioned agents, in case of a future approval. Regardless of its clinical uptake, it should be noted that the development of margetuximab has relevantly improved our biological understanding of HER2-positive BC, highlighting the implication of patient's genotype in determining treatment outcomes, as well as the relevance of antibody-dependent cellular cytotoxicity (ADCC) in the context of HER2-blockade.
目前，对于接受双重HER2阻断治疗及曲妥珠单抗（ado）曲妥珠单抗（TDM-1）后病情进展的HER2阳性晚期乳腺癌（BC）患者，尚无推荐的特定标准治疗方案。然而，几种新型抗HER2药物正在涌现，并迅速改变这一局面。其中，Fc工程单克隆抗体玛格妥昔单抗最近显示，在与化疗联合用于经治的HER2阳性晚期BC时，与曲妥珠单抗相比，可略微改善无进展生存期（PFS）。
本综述文章概述了玛格妥昔单抗的临床开发情况，批判性地讨论了其在当前BC治疗算法格局中的意义。
玛格妥昔单抗的临床作用只能结合经治的HER2阳性晚期BC快速演变的治疗格局来解读。事实上，最近获批的抗HER2药物图卡替尼和曲妥珠单抗（德）曲妥珠单抗目前是TDM1治疗后环境中颇具吸引力的选择，而玛格妥昔单抗在未来获批的情况下，可能在上述药物进展后发挥作用。无论其临床应用情况如何，值得注意的是，玛格妥昔单抗的开发显著提高了我们对HER2阳性BC的生物学理解，突出了患者基因型在决定治疗结果中的作用，以及抗体依赖性细胞毒性（ADCC）在HER2阻断背景下的相关性。
