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Pertuzumab: Evolving therapeutic strategies in the management of HER2-overexpressing breast cancer

机译：帕妥珠单抗：HER2过表达乳腺癌管理中不断发展的治疗策略

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Introduction: HER2 overexpression or amplification is present in approximately one-fifth of breast cancers and historically was associated with aggressive disease and poorer prognosis. The introduction of the humanized monoclonal antibody trastuzumab dramatically improved disease-free survival (DFS) and overall survival (OS) in this subgroup. As the majority of patients with metastatic disease ultimately develop resistance to trastuzumab, a need exists for more effective targeted therapies. Pertuzumab is an anti-HER2eu-targeted therapy in the late stages of clinical development. The combination of pertuzumab, trastuzumab and docetaxel has been found to have an OS benefit in patients with HER2 positive metastatic breast cancer (MBC) when used in the first-line setting. This reflects a new standard of care, and pertuzumab was recently approved for this indication by the Food and Drug Administration (FDA). The efficacy of pertuzumab and trastuzumab in conjunction with chemotherapy is currently being evaluated in the adjuvant setting. Areas covered: This article provides an overview of preclinical investigations in addition to reviewing pertinent Phase I, Phase II and Phase III clinical trials. Expert opinion: Pertuzumab, in combination with the humanized monoclonal antibody trastuzumab, and docetaxel is a standard of care for patients with previously untreated metastatic breast cancer based on the CLEOPATRA study showing a survival benefit. There is no increase in cardiac toxicity with the combined HER2-targeted therapy. Future issues will address appropriate sequencing and combination with other anti-HER2-targeted therapies and/or chemotherapy.
机译：简介：HER5的过度表达或扩增存在于大约五分之一的乳腺癌中，历史上与侵袭性疾病和较差的预后有关。人源化单克隆抗体曲妥珠单抗的引入大大改善了该亚组的无病生存期（DFS）和总体生存期（OS）。由于大多数患有转移性疾病的患者最终发展出对曲妥珠单抗的耐药性，因此需要更有效的靶向治疗。帕妥珠单抗是临床开发后期的抗HER2 / neu靶向治疗。已发现在第一线治疗中使用帕妥珠单抗，曲妥珠单抗和多西他赛的组合对HER2阳性转移性乳腺癌（MBC）患者具有OS益处。这反映了一种新的护理标准，并且pertuzumab最近被美国食品药品管理局（FDA）批准用于该适应症。目前正在佐剂环境中评估帕妥珠单抗和曲妥珠单抗联合化疗的疗效。涵盖的领域：本文概述了临床前研究，并回顾了相关的I期，II期和III期临床试验。专家意见：基于CLEOPATRA的研究显示，帕妥珠单抗与人源化单克隆抗体曲妥珠单抗和多西他赛联合使用是以前未经治疗的转移性乳腺癌患者的治疗标准，显示出生存获益。靶向HER2的联合治疗不会增加心脏毒性。未来的问题将解决适当的测序以及与其他抗HER2靶向治疗和/或化疗的组合。

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