INTRODUCTION T-DM1 has been approved for the treatment of HER2+ breast cancer. Cardiac dysfunction is a side effect of trastuzumab, a component of T-DM1. However, little is known about T-DM1-associated cardiotoxicity. METHODS We have conducted a pooled analysis of T-DM1 trials in advanced HER2+ breast cancer cases to understand the incidence, clinical presentation as well as to establish possible risk factors for T-DM1-associated cardiotoxicity. The primary endpoint was the incidence of cardiac events (CEs). CEs were categorized as follows: (1) congestive heart failure (CHF) or grade 3/4 LVEF drop; (2) cardiac ischemia, (3) cardiac arrhythmia, (4) grade 1/2 LVEF drop. Secondary endpoints included CE recovery rate and impact of CEs on treatment discontinuation. Logistic regression was used to assess possible risk factors for CEs. RESULTS Individual patient-level data from 1961 patients exposed to T-DM1 in seven trials were pooled. Of these, 1544 received T-DM1 and 417 T-DM1 + pertuzumab. CHF/LVEF drop grade 3/4 was reported in 0.71%, cardiac ischemia in 0.1%, cardiac arrhythmia in 0.71% and grade 1/2 LVEF drop in 2.04%. The total CE rate was 3.37% (95% confidence interval (CI), 2.6%-4.3%). Multivariate analysis showed patient's age ≥65 (OR 3.0; 95% CI, 1.77-5.14; P-value <0.001) and baseline LVEF<55% (OR 2.62; 95% CI, 1.29-5.32; P-value 0.008) as risk factors. CEs resolved in most (79%) patients after treatment discontinuation. CONCLUSION The incidence of CEs in patients receiving T-DM1 was low. Older patients receiving T-DM1 should be carefully followed for cardiac safety during treatment.

中文翻译：

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曲妥珠单抗Emtansine（T-DM1）相关的心脏毒性：晚期HER2阳性乳腺癌的汇总分析。

简介T-DM1已被批准用于治疗HER2 +乳腺癌。心脏功能障碍是曲妥珠单抗（T-DM1的一种成分）的副作用。然而，关于T-DM1相关的心脏毒性知之甚少。方法我们对晚期HER2 +乳腺癌病例中的T-DM1试验进行了汇总分析，以了解其发生率，临床表现以及建立与T-DM1相关的心脏毒性的可能危险因素。主要终点是心脏事件（CE）的发生率。CE的分类如下：（1）充血性心力衰竭（CHF）或3/4 LVEF下降；（2）心脏缺血，（3）心脏心律不齐，（4）1/2 LVEF下降。次要终点包括CE的恢复率和CE对治疗中断的影响。Logistic回归用于评估CE的可能危险因素。结果汇总了七项试验中1961年暴露于T-DM1的患者的个体患者水平数据。其中1544例接受了T-DM1，417例接受了T-DM1 +帕妥珠单抗。报道CHF / LVEF下降3/4级为0.71％，心脏缺血为0.1％，心律不齐为0.71％，1/2 LVEF下降为2.04％。总CE率为3.37％（95％置信区间（CI），2.6％-4.3％）。多变量分析显示患者年龄≥65（OR 3.0; 95％CI，1.77-5.14; P值<0.001）和基线LVEF <55％（OR 2.62; 95％CI，1.29-5.32; P值0.008）为风险因素。停药后，大多数（79％）患者的CE消退。结论接受T-DM1的患者中CE的发生率较低。接受T-DM1的老年患者在治疗期间应注意心脏安全。