Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study
Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study
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DOI：
10.1016/s0140-6736(11)60070-6
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发表时间：
2011-03-12
期刊：
影响因子：
168.9
通讯作者：
Twelves, Chris
中科院分区：
文献类型：
--
作者：
Cortes, Javier;O'Shaughnessy, Joyce;Twelves, Chris
背景：对于接受过大量预治疗的转移性乳腺癌患者，非常需要具有生存益处的治疗。甲磺酸艾日布林是一种新型的非紫杉烷类微管动力学抑制剂。我们的目的是比较接受艾日布林与目前可用的treatment.Methods在这个3期开放标签研究中，局部复发或转移性乳腺癌的妇女被随机分配（2：1）到甲磺酸艾日布林（1.4 mg/m2）静脉内给药2-5分钟，21天周期的第8天和第8天）或治疗医生的选择（TPC）。患者既往接受过2 - 5种化疗方案（晚期患者接受过2种或更多种），包括蒽环类和紫杉烷类，除非有禁忌症。根据地理区域、既往卡培他滨治疗和人表皮生长因子受体2状态对随机化进行分层。患者和研究者对治疗分配不设盲。主要终点是意向治疗人群的总生存期。该研究在ClinicalTrials.gov注册，编号NCT 00388726。结果762名妇女被随机分配到治疗组（508名艾日布林，254名TPC）。与TPC组（10.6个月，9.3-12.5;风险比0.81，95%CI 0.66-0.99; p=0.041）相比，分配至艾日布林组（中位数13.1个月，95%CI 11.8-14.3）的女性的总生存期显著改善。两组中最常见的不良事件是虚弱或疲劳（所有等级的503例艾日布林患者中的270例[54%]和247例TPC患者中的98例[40%]）和中性粒细胞减少症（所有等级的260例艾日布林患者和73例TPC患者中的73例[30%]）。周围神经病变是导致艾日布林停药的最常见不良事件，503例患者中有24例（5%）发生。这一发现挑战了在难治性环境中评价新抗癌疗法期间改善总生存期是不切实际的期望的概念。
Background Treatments with survival benefit are greatly needed for women with heavily pretreated metastatic breast cancer. Eribulin mesilate is a non-taxane microtubule dynamics inhibitor with a novel mode of action. We aimed to compare overall survival of heavily pretreated patients receiving eribulin versus currently available treatments.Methods In this phase 3 open-label study, women with locally recurrent or metastatic breast cancer were randomly allocated (2:1) to eribulin mesilate (1.4 mg/m(2) administered intravenously during 2-5 min on days land 8 of a 21-day cycle) or treatment of physician's choice (TPC). Patients had received between two and five previous chemotherapy regimens (two or more for advanced disease), including an anthracycline and a taxane, unless contraindicated. Randomisation was stratified by geographical region, previous capecitabine treatment, and human epidermal growth factor receptor 2 status. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00388726.Findings 762 women were randomly allocated to treatment groups (508 eribulin, 254 TPC). Overall survival was significantly improved in women assigned to eribulin (median 13.1 months, 95% CI 11.8-14.3) compared with TPC (10.6 months, 9.3-12.5; hazard ratio 0.81,95% CI 0.66-0.99; p=0.041). The most common adverse events in both groups were asthenia or fatigue (270 [54%] of 503 patients on eribulin and 98 [40%] of 247 patients on TPC at all grades) and neutropenia (260 [52%] patients receiving eribulin and 73 [30%] of those on TPC at all grades). Peripheral neuropathy was the most common adverse event leading to discontinuation from eribulin, occurring in 24 (5%) of 503 patients.Interpretation Eribulin showed a significant and clinically meaningful improvement in overall survival compared with TPC in women with heavily pretreated metastatic breast cancer. This finding challenges the notion that improved overall survival is an unrealistic expectation during evaluation of new anticancer therapies in the refractory setting.