Open-Label, Phase II, Multicenter, Randomized Study of the Efficacy and Safety of Two Dose Levels of Pertuzumab, a Human Epidermal Growth Factor Receptor 2 Dimerization Inhibitor, in Patients With Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer
Open-Label, Phase II, Multicenter, Randomized Study of the Efficacy and Safety of Two Dose Levels of Pertuzumab, a Human Epidermal Growth Factor Receptor 2 Dimerization Inhibitor, in Patients With Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer
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DOI：
10.1200/jco.2009.24.1661
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发表时间：
2010-03-01
影响因子：
45.3
通讯作者：
Baselga, Jose
中科院分区：
文献类型：
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作者：
Gianni, Luca;Llado, Anna;Baselga, Jose
目的：帕妥珠单抗是一种抑制人表皮生长因子受体2 （HER2）二聚化的人源化单克隆抗体。该II期试验的目的是评估帕妥珠单抗单药治疗her2阴性转移性乳腺癌患者的抗肿瘤活性和安全性。还探讨了在石蜡包埋组织中检测到的生物标志物作为反应预测因子的效用。患者和方法这是一项国际、多中心、开放标签、随机II期研究。中心确诊的her2阴性转移性乳腺癌患者（n = 79）被随机分配每3周接受一次帕妥珠单抗治疗，负荷剂量为840mg，随后接受420mg （a组）或1050mg （B组）。患者按国家和既往紫杉烷治疗进行分层。结果在随机分配的79例患者中，78例纳入意向治疗人群。在A组（n = 41）中，2例患者部分缓解，18例患者（44%）经历了持续>= 12周的疾病稳定（SD）。在B组（n = 37）中，14例（38%）患者出现SD。总体而言，78例患者中有6例在6个月后缓解或出现SD。帕妥珠单抗总体耐受性良好，大多数不良事件为轻度至中度。8例患者左心室射血分数下降>= 10%和/或低于50%，a组1例充血性心力衰竭，药代动力学数据支持每3周一次固定剂量的帕妥珠单抗。结论本研究中观察到的有限疗效，通常是持续时间相对较短的SD，表明进一步研究单药帕妥珠单抗对未选择的her2阴性疾病患者的益处不大。中华临床杂志，28(3):391 - 391。(C) 2010年由美国临床肿瘤学会出版
PurposePertuzumab is a humanized monoclonal antibody inhibiting human epidermal growth factor receptor 2 (HER2) dimerization. The aim of this phase II trial was to assess the antitumor activity and safety profile of pertuzumab monotherapy in patients with HER2-negative metastatic breast cancer. The utility of biomarkers detected in paraffin-embedded tissue as predictors of response was also explored.Patients and MethodsThis was an international, multicenter, open-label, randomized phase II study. Patients (n = 79) with centrally confirmed HER2-negative metastatic breast cancer were randomly assigned to receive pertuzumab once every 3 weeks with a loading dose of 840 mg followed thereafter by either 420 mg (arm A) or 1,050 mg (arm B). Patients were stratified by country and prior taxane therapy.ResultsOf 79 patients who were randomly assigned, 78 were included in the intent-to-treat population. In arm A (n = 41), two patients had partial responses, and 18 patients (44%) experienced stable disease (SD) lasting >= 12 weeks. In arm B (n = 37), SD was observed in 14 patients (38%). Overall, six of 78 patients responded or had SD >= 6 months. Pertuzumab was generally well tolerated, and most adverse events were mild to moderate. Decline in left ventricular ejection fraction of >= 10% and/or to less than 50% was observed in eight patients, with one case of congestive heart failure in arm A. Pharmacokinetic data supported a fixed dose of pertuzumab once every 3 weeks.ConclusionThe limited efficacy observed in this study, generally SD of relatively short duration, suggested little benefit of further investigation of single-agent pertuzumab in unselected patients with HER2-negative disease. J Clin Oncol 28: 1131-1137. (C) 2010 by American Society of Clinical Oncology