Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study
Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study
复制标题
DOI：
10.1007/s10549-019-05191-2
复制
发表时间：
2019-06-01
影响因子：
3.8
通讯作者：
Swain, S. M.
中科院分区：
文献类型：
--
作者：
Lynce, F.;Barac, A.;Swain, S. M.
目的HER 2靶向治疗显著改善了乳腺癌患者的预后，但也可能导致心脏毒性。指南建议暂停HER 2靶向治疗，直至心功能障碍消退。SAFE-HEaRt是第一个试验，前瞻性地测试这些治疗是否可以安全地管理，而不中断患者的心功能不全。MethodsPatients与阶段I-IV HER 2阳性乳腺癌候选人曲妥珠单抗，帕妥珠单抗或阿多-曲妥珠单抗emtansine（TDM-1），左心室射血分数（LVEF）40-49%，没有心力衰竭（HF）的症状。所有患者均接受心脏病学访视、连续超声心动图检查，并接受β受体阻滞剂和ACE抑制剂治疗，除非有禁忌症。主要终点是完成计划的HER 2靶向治疗，未发生心脏事件（CE）（定义为HF、心肌梗死、心律失常或心源性死亡）或LVEF显著无症状恶化。如果计划的肿瘤治疗完成率至少为30%，则认为该研究是成功的。15例患者接受曲妥珠单抗治疗，14例接受曲妥珠单抗和帕妥珠单抗治疗，2例接受TDM-1治疗。基线时平均LVEF为45%，治疗结束时为46%。27例患者（90%）完成了计划的HER 2靶向治疗。2例患者发生CE，1例患者LVEF无症状恶化至35%.ConclusionThis study provides safety data of HER 2-targeted therapies in patients with breast cancer and reduced LVEF while receiving cardioprotective medications and close heart monitoring.我们的研究结果表明，心脏病学和肿瘤学提供者之间的合作的重要性，以允许提供最佳的肿瘤护理，这一独特的人群。
PurposeHER2-targeted therapies have substantially improved the outcome of patients with breast cancer, however, they can be associated with cardiac toxicity. Guidelines recommend holding HER2-targeted therapies until resolution of cardiac dysfunction. SAFE-HEaRt is the first trial that prospectively tests whether these therapies can be safely administered without interruptions in patients with cardiac dysfunction.MethodsPatients with stage I-IV HER2-positive breast cancer candidates for trastuzumab, pertuzumab or ado-trastuzumab emtansine (TDM-1), with left ventricular ejection fraction (LVEF) 40-49% and no symptoms of heart failure (HF) were enrolled. All patients underwent cardiology visits, serial echocardiograms and received beta blockers and ACE inhibitors unless contraindicated. The primary endpoint was completion of the planned HER2-targeted therapies without developing either a cardiac event (CE) defined as HF, myocardial infarction, arrhythmia or cardiac death or significant asymptomatic worsening of LVEF. Thestudy was considered successful if planned oncology therapy completion rate was at least 30%.ResultsOf 31 enrolled patients, 30 were evaluable. Fifteen patients were treated with trastuzumab, 14 with trastuzumab and pertuzumab, and 2 with TDM-1. Mean LVEF was 45% at baseline and 46% at the end of treatment. Twenty-seven patients (90%) completed the planned HER2-targeted therapies. Two patients experienced a CE and 1 had an asymptomatic worsening of LVEF to 35%.ConclusionThis study provides safety data of HER2-targeted therapies in patients with breast cancer and reduced LVEF while receiving cardioprotective medications and close cardiac monitoring. Our results demonstrate the importance of collaboration between cardiology and oncology providers to allow for delivery of optimal oncologic care to this unique population.