ABSTRACT

Introduction

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.

Areas covered

The present review article recapitulates the clinical development of margetuximab, critically discussing its implications in the current landscape of BC treatment algorithms.

Expert opinion

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.

中文翻译：

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Margetuximab 用于治疗 HER2 阳性转移性乳腺癌

摘要

介绍

对于进展为双重 HER2 阻断剂和曲妥珠单抗 (TDM-1) 的 HER2 阳性晚期乳腺癌 (BC) 患者，目前没有推荐特定的标准治疗。然而，一些新型抗 HER2 药物正在出现并迅速改变了这种情况。其中，FC 工程化的单克隆抗体 margetuximab 最近证明，与曲妥珠单抗相比，当与化疗联合治疗预处理的 HER2 阳性晚期 BC 时，可略微提高无进展生存期 (PFS)。

覆盖区域

本综述文章概括了 margetuximab 的临床发展，批判性地讨论了其在 BC 治疗算法当前格局中的影响。

专家意见

Margetuximab 的临床作用只能根据预先治疗的 HER2 阳性晚期 BC 的快速发展的治疗前景来解释。事实上，最近批准的抗 HER2 药物 tucatinib 和曲妥珠单抗 deruxtecan 目前代表了 TDM1 后环境的有吸引力的选择，而在未来批准的情况下，margetuximab 可能在进展为上述药物后发挥作用。不管其临床应用如何，应该指出的是，margetuximab 的开发相关地提高了我们对 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意义，以及抗体依赖性细胞毒性的相关性。 ADCC) 在 HER2 阻断的背景下。