CLEOPATRA: A Phase III Evaluation of Pertuzumab and Trastuzumab for HER2-Positive Metastatic Breast Cancer
CLEOPATRA: A Phase III Evaluation of Pertuzumab and Trastuzumab for HER2-Positive Metastatic Breast Cancer
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DOI：
10.3816/cbc.2010.n.065
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发表时间：
2010-12-01
影响因子：
3.1
通讯作者：
Swain, Sandra M.
中科院分区：
文献类型：
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作者：
Baselga, Jose;Swain, Sandra M.
简介：人表皮生长因子受体2（HER2）阳性乳腺癌患者预后较差。尽管曲妥珠单抗治疗标准已被证明有效，但大多数 HER2 阳性转移性乳腺癌 (MBC) 患者最终都会出现进展，需要进一步干预以延长生命。帕妥珠单抗是一种人源化单克隆抗体，是第一个 HER2 二聚化抑制剂。它与 HER2 结构域上的二聚化位点结合，防止配体驱动的 HER2 与其他 HER 受体配对，从而抑制肿瘤细胞的生长和存活。因此，曲妥珠单抗和帕妥珠单抗的组合可以更全面地阻断 HER 信号通路，从而产生更大的抗肿瘤功效。研究设计：CLEOPATRA（帕妥珠单抗和曲妥珠单抗的临床评估）是一项国际、随机、双盲、安慰剂对照 III 期试验，旨在招募来自全球约 250 个中心的约 800 名患者。患有局部复发或转移性疾病的 HER2 阳性乳腺癌成人患者将被随机 (1:1) 接受多西他赛、曲妥珠单抗和帕妥珠单抗治疗，或多西他赛、曲妥珠单抗和安慰剂治疗。该研究的主要终点是无进展生存期（PFS），基于独立审查机构进行的肿瘤评估。次要终点包括研究者评估评估的 PFS、总体生存率、客观缓解率、缓解持续时间、症状进展时间和安全性。还将收集数据以确定可能与临床结果相关的生物标志物。结论：CLEOPATRA 研究将提供有关在 HER2 阳性 MBC 患者的现行护理标准中添加帕妥珠单抗的有效性和安全性的重要信息。
Introduction: Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer have a poor prognosis. Despite proven efficacy with the standard of care, trastuzumab, most patients with HER2-positive metastatic breast cancer (MBC) will eventually progress, requiring further intervention to prolong life. Pertuzumab, a humanized monoclonal antibody, is the first HER2 dimerization inhibitor. It binds to the dimerization site on the HER2 domain and prevents ligand-driven pairing of HER2 with other HER receptors, thus inhibiting tumor cell growth and survival. Combining trastuzumab and pertuzumab therefore provides a more comprehensive blockade of the HER signaling pathways, resulting in greater antitumor efficacy. Study Design: CLEOPATRA (CLinical Evaluation Of Pertuzumab And TRAstuzumab) is an international, randomized, double-blind, placebo-controlled phase III trial that aims to recruit approximately 800 patients from around 250 centers worldwide. Adults with HER2-positive adenocarcinoma of the breast with locally recurrent or metastatic disease will be randomized (1:1) to receive docetaxel, trastuzumab, and pertuzumab or docetaxel, trastuzumab, and placebo. The primary endpoint of the study is progression-free survival (PFS), based on tumor assessments conducted by an independent review facility. Secondary endpoints include PFS evaluated by investigator assessment, overall survival, objective response rate, duration of response, time to symptom progression, and safety. Data will also be collected to identify biomarkers that may correlate with clinical outcomes. Conclusion: The CLEOPATRA study will provide important information about the efficacy and safety of adding pertuzumab to one current standard of care in patients with HER2-positive MBC.