Ankara Numune Education and Research Hospital, Department of Medical Oncology, Ankara, Turkey.
Curr Med Res Opin. 2012 Oct;28(10):1709-16. doi: 10.1185/03007995.2012.728132. Epub 2012 Oct 11.
Lack of response in some patients and relapse during the course of therapy in the treatment of HER2-positive early breast cancer and metastatic breast cancer continue to challenge researchers and clinicians towards a better understanding of the fundamental mechanisms of trastuzumab action and new therapies for HER2. The aim of this review is to discuss current and future treatment options with pertuzumab in the light of new insights into HER2-positive breast cancer.
Pertuzumab showed positive results in clinical studies and agents in routine clinical usage are updated. The PubMed database, ASCO and San Antonio Breast Cancer Symposium Meeting abstracts were searched up to June 2012 by using the terms 'pertuzumab' and 'anti-HER2 treatment'; papers which were considered relevant for the aim of this review were selected by the authors.
The presented trials of phase II and phase III randomized trials of CLEOPATRA, NEOSPHERE and TRYPHAENA have showed pertuzumab action to be complementary to trastuzumab without increasing adverse events. Adding pertuzumab to trastuzumab in the first line of HER2-positive metastatic breast cancer and in the neoadjuvant treatment of locally advanced HER2-positive breast cancer is usually well tolerated. The evaluation of health-related quality of life showed that combining pertuzumab with docetaxel and trastuzumab compared to placebo have no detrimental effect with adding pertuzumab.
Pertuzumab is the first HER dimerization inhibitor with a mechanism of action complementary to trastuzumab. Studies with anti-HER2 combination treatments indicate that the use of more than one HER2-targeted therapy was superior to one of these agents alone. Pertuzumab has produced impressive anti-tumor activity in combination with trastuzumab. There are ongoing studies with pertuzumab with an increasing tendency towards moving the study of these agents to earlier stages of the disease, namely in the adjuvant and neoadjuvant setting.
曲妥珠单抗治疗 HER2 阳性早期乳腺癌和转移性乳腺癌的过程中，部分患者无应答或出现复发，这一现象一直困扰着研究人员和临床医生，促使他们深入了解曲妥珠单抗作用的基本机制，并寻找新的 HER2 治疗方法。本文旨在结合 HER2 阳性乳腺癌的新认识，探讨目前和未来使用帕妥珠单抗的治疗选择。
帕妥珠单抗在临床试验中取得了阳性结果，且常规临床应用的药物也在不断更新。本研究检索了截至 2012 年 6 月在 PubMed 数据库、ASCO 年会和圣安东尼奥乳腺癌研讨会摘要中使用“pertuzumab”和“抗 HER2 治疗”等术语发表的相关文献，并由作者筛选出与本综述目的相关的文献。
CLEOPATRA、NEOSPHERE 和 TRYPHAENA 这两项 II 期和 III 期随机试验显示，帕妥珠单抗与曲妥珠单抗联合应用可增强疗效而不增加不良反应。在 HER2 阳性转移性乳腺癌的一线治疗和局部晚期 HER2 阳性乳腺癌的新辅助治疗中，曲妥珠单抗联合帕妥珠单抗通常具有良好的耐受性。对健康相关生活质量的评估表明，与安慰剂相比，帕妥珠单抗联合多西他赛和曲妥珠单抗不会产生不利影响。
帕妥珠单抗是首个具有与曲妥珠单抗作用机制互补的 HER 二聚化抑制剂。抗 HER2 联合治疗研究表明，与单一药物相比，使用多种 HER2 靶向药物治疗具有更好的疗效。帕妥珠单抗与曲妥珠单抗联合具有显著的抗肿瘤活性。目前正在进行帕妥珠单抗的相关研究，且有将这些药物研究向疾病早期阶段（即辅助和新辅助治疗）推进的趋势。
