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曲妥珠单抗治疗 HER2 阳性乳腺癌的心脏毒性meta 分析

Cardiac toxicities of lapatinib in patients with breast cancer and other HER2-positive cancers: a meta-analysis.

机构信息

College of Pharmacy, Yeungnam University, 280 Daehak-ro, Gyeongsan, Gyeongsangbuk-do, 38541, Republic of Korea.

College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea.

出版信息

Breast Cancer Res Treat. 2017 Dec;166(3):927-936. doi: 10.1007/s10549-017-4460-9. Epub 2017 Aug 19.

Abstract

PURPOSE

Lapatinib is a tyrosine kinase inhibitor that targets the human epidermal growth factor receptor 2 (HER2) and the epidermal growth factor receptor (EGFR/HER1), and there are concerns about its cardiac toxicity. Recent studies of lapatinib have reported cardiac adverse events; however, the results have been inconsistent among the studies. The aim of our study was to estimate the cardiac toxicity of lapatinib in patients with breast cancer and other HER2-positive cancers.

METHODS

To evaluate the cardiotoxicity of lapatinib, the results of previous studies were quantitatively integrated using meta-analysis. Forty-five articles regarding cardiac adverse events, including left ventricular dysfunction, left ventricular ejection fraction (LVEF) decrease, arrhythmia, and other cardiac adverse events, were assessed. As a subgroup analysis in patients with breast cancer, 26 studies of lapatinib-induced cardiac adverse events were assessed.

RESULTS

The overall incidence of cardiac adverse events was 2.70% (95% confidence interval [CI] 1.60-4.50%). The incidences of left ventricular dysfunction and LVEF decrease were 1.60% (95% CI 1.30-2.00%) and 2.20% (95% CI 1.30-3.60%), respectively. The overall incidence of cardiac adverse events was 3.00% (95% CI 1.50-6.10%) in patients with breast cancer, which was marginally higher than the rate in patients with all type of cancers.

CONCLUSION

The overall incidence of lapatinib-induced cardiac toxicity was relatively low based on an indirect comparison with trastuzumab. However, careful monitoring of cardiac toxicity is still needed when patients are treated with lapatinib because the related risk factors have not been clearly identified.

摘要

目的

拉帕替尼是一种针对人表皮生长因子受体 2(HER2)和表皮生长因子受体(EGFR/HER1)的酪氨酸激酶抑制剂,存在心脏毒性方面的担忧。最近的拉帕替尼研究报告了心脏不良事件,但研究结果并不一致。本研究旨在评估拉帕替尼治疗乳腺癌和其他 HER2 阳性癌症患者的心脏毒性。

方法

为评估拉帕替尼的心脏毒性,采用荟萃分析对以往研究结果进行定量综合。评估了 45 篇关于心脏不良事件的文章,包括左心室功能障碍、左心室射血分数(LVEF)下降、心律失常和其他心脏不良事件。作为乳腺癌患者的亚组分析,评估了 26 项拉帕替尼引起的心脏不良事件研究。

结果

心脏不良事件的总发生率为 2.70%(95%置信区间[CI] 1.60-4.50%)。左心室功能障碍和 LVEF 下降的发生率分别为 1.60%(95% CI 1.30-2.00%)和 2.20%(95% CI 1.30-3.60%)。乳腺癌患者的心脏不良事件总发生率为 3.00%(95% CI 1.50-6.10%),略高于所有类型癌症患者的发生率。

结论

与曲妥珠单抗间接比较,拉帕替尼引起的心脏毒性总发生率相对较低。然而,当患者接受拉帕替尼治疗时,仍需密切监测心脏毒性,因为相关的危险因素尚未明确。

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