Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Drugs Today (Barc). 2021 Sep;57(9):551-558. doi: 10.1358/dot.2021.57.9.3319148.
Up to 20% of breast cancers overexpress HER2, a molecular alteration conferring these tumors a particularly aggressive behavior. However, targeting HER2 has radically changed the prognosis of this disease in the last 2 decades, with multiple anti-HER2 compounds shown to improve disease outcomes both in the early and advanced setting. The latest anti-HER2 compound to be approved by the U.S. Food and Drug Administration (FDA) was margetuximab, an Fc-engineered monoclonal antibody with an improved binding to FcγRIIIA receptor, which leads to a greater antibody-dependent cellular cytotoxicity (ADCC) activation compared with trastuzumab. Margetuximab was shown to slightly improve progression-free survival compared with trastuzumab when combined with chemotherapy for the treatment of advanced HER2-positive breast cancer patients, and is now included among the available treatment options for pretreated HER2-positive breast cancer patients. In this monograph we recapitulate the clinical development, current role and future perspectives of margetuximab for the treatment of breast cancer.
高达 20%的乳腺癌过表达 HER2，这种分子改变使这些肿瘤具有特别侵袭性的行为。然而，针对 HER2 的治疗在过去 20 年中彻底改变了这种疾病的预后，多种抗 HER2 化合物已被证明可改善早期和晚期疾病的结局。最近由美国食品和药物管理局 (FDA) 批准的抗 HER2 化合物是玛格替昔单抗，这是一种 Fc 工程化的单克隆抗体，与 FcγRIIIA 受体的结合得到改善，与曲妥珠单抗相比，抗体依赖性细胞毒性 (ADCC) 的激活更强。玛格替昔单抗联合化疗治疗晚期 HER2 阳性乳腺癌患者时，与曲妥珠单抗相比，可略微改善无进展生存期，现已被纳入 HER2 阳性乳腺癌患者的治疗选择之一。在本专论中，我们回顾了玛格替昔单抗治疗乳腺癌的临床开发、当前作用和未来前景。
