Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial
Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial
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DOI：
10.1200/jco.2006.09.1611
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发表时间：
2007-09-01
影响因子：
45.3
通讯作者：
Piccart-Gebhart, Martine J.
中科院分区：
文献类型：
--
作者：
Suter, Thomas M.;Procter, Marion;Piccart-Gebhart, Martine J.
目的：本分析的目的是调查曲妥珠单抗在乳腺癌患者完成（新）辅助化疗（伴或不伴放疗）后的心脏不良反应。患者和方法Herceptin佐剂（HERA）试验是一项三组、多中心、开放标签随机试验，比较了每3周给药1次或2年曲妥珠单抗与观察her -2阳性乳腺癌患者的疗效。只有完成（新）辅助化疗（伴或不伴放疗）后左室射血分数正常（LVEF >= 55%）的患者才符合条件。心功能不全时复查LVEF。结果1693例患者随机分配到1年曲妥珠单抗组，1693例患者随机分配到观察组。曲妥珠单抗因心脏疾病而停药的发生率很低（4.3%）。与观察组相比，曲妥珠单抗组心脏终点发生率更高（严重充血性心力衰竭[CHF]， 0.60% v 0.00%；症状性CHF， 2.15% v 0.12%；确认LVEF显著下降，3.04% v 0.53%）。大多数心功能障碍患者在6个月内恢复。曲妥珠单抗相关性心功能障碍患者接受更高累积剂量的阿霉素(287 mg/m（2) v 257 mg/m(2)）或表阿霉素(480 mg/m（2) v 422 mg/m(2)）治疗，筛查LVEF较低，体重指数较高。结论：考虑到无病生存期的明显获益、心脏不良事件的低发生率以及心功能障碍可能可逆的提示，对于符合HERA试验资格标准的乳腺癌患者，应考虑使用曲妥珠单抗作为辅助治疗。
PurposeThe purpose of this analysis was to investigate trastuzumab- associated cardiac adverse effects in breast cancer patients after completion of ( neo) adjuvant chemotherapy with or without radiotherapy.Patients and MethodsThe Herceptin Adjuvant ( HERA) trial is a three- group, multicenter, open- label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2-positive breast cancer. Only patients who after completion of ( neo) adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction ( LVEF >= 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction.ResultsData were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low ( 4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation ( severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin ( 287 mg/m(2) v 257 mg/m(2)) or epirubicin ( 480 mg/m(2) v 422 mg/m(2)) and had a lower screening LVEF and a higher body mass index.ConclusionGiven the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria.