University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94115, USA.
Expert Opin Drug Saf. 2010 Mar;9(2):335-46. doi: 10.1517/14740331003627441.
Trastuzumab has become a mainstay in the treatment of women with human epidermal growth factor receptor-2 (HER2)-overexpressing breast cancer in the metastatic and adjuvant settings. Although trastuzumab is generally well tolerated, cardiac toxicity has emerged as a rare but potentially serious complication that limits its use in some patients. It is critically important to understand the nature of this cardiac risk when counseling patients, especially as new anti-HER2 agents are developed and tested in combination with trastuzumab.
This review describes the incidence, risk factors and natural history of trastuzumab-associated cardiac toxicity reported in updated efficacy and cardiac safety analyses of metastatic and adjuvant trastuzumab clinical trials. Mechanisms of trastuzumab-associated cardiotoxicity are proposed and compared to what is known about anthracycline-induced cardiotoxicity. The existing cardiac safety data for lapatinib and other newer HER2-targeted therapies are also discussed, both as single agents and in combination with trastuzumab.
The reader will gain a comprehensive understanding of the existing cardiac safety data for trastuzumab including the notable differences in trial design and study populations between each of the major adjuvant trials. Readers will become familiar with the risk factors associated with trastuzumab-induced cardiotoxicity as well as with the natural history of its course.
The majority of trastuzumab-related cardiac events observed have been asymptomatic declines in left ventricular ejection fraction. The incidence of severe congestive heart failure and cardiac death observed in the large adjuvant trastuzumab trials ranges from 0.6 to 4%. Both symptomatic and asymptomatic events are largely reversible and manageable; however, little is known about the significance of asymptomatic left ventricular ejection fraction decline and longer cardiac follow-up is needed. Close cardiac monitoring must be performed for all patients receiving anti-HER2 agents currently in the clinic or in development.
曲妥珠单抗已成为人表皮生长因子受体-2（HER2）过表达转移性和辅助性乳腺癌治疗的主要手段。尽管曲妥珠单抗通常耐受性良好，但心脏毒性已成为一种罕见但潜在严重的并发症，限制了其在某些患者中的应用。在为患者提供咨询时，了解这种心脏风险的性质至关重要，尤其是当新的抗 HER2 药物与曲妥珠单抗联合开发和测试时。
本篇综述描述了在转移性和辅助性曲妥珠单抗临床试验的疗效和心脏安全性更新分析中报告的曲妥珠单抗相关心脏毒性的发生率、危险因素和自然史。提出了曲妥珠单抗相关心脏毒性的机制，并将其与蒽环类药物引起的心脏毒性进行了比较。还讨论了拉帕替尼和其他新型 HER2 靶向治疗的现有心脏安全性数据，包括作为单一药物以及与曲妥珠单抗联合使用的数据。
读者将全面了解曲妥珠单抗的现有心脏安全性数据，包括每个主要辅助试验在试验设计和研究人群方面的显著差异。读者将熟悉与曲妥珠单抗诱导的心脏毒性相关的危险因素以及其病程的自然史。
观察到的大多数曲妥珠单抗相关心脏事件都是左心室射血分数无症状下降。在大型辅助性曲妥珠单抗试验中观察到的充血性心力衰竭和心脏死亡的发生率为 0.6%至 4%。有症状和无症状的事件在很大程度上是可逆和可管理的；然而，对于无症状左心室射血分数下降的意义知之甚少，需要进行更长时间的心脏随访。目前正在临床使用或开发中的所有接受抗 HER2 药物治疗的患者都必须进行密切的心脏监测。
