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曲妥珠单抗诱导的HER-2阳性老年乳腺癌女性心脏毒性:真实世界数据的荟萃分析

Trastuzumab-induced cardiotoxicity in elderly women with HER-2-positive breast cancer: a meta-analysis of real-world data.

作者信息

Leung Henry W C, Chan Agnes L F

机构信息

a 1 China Medical University-An Nan Hospital, Department of Radiation Therapy , No. 66, Sec. 2, Changhe Rd, Annan Dist, Tainan, Taiwan.

b 2 China Medical University-An-Nan Hospital, Department of Pharmacy , No. 66, Sec. 2, Changhe Rd, Annan Dist, Tainan, Taiwan +886 63 55 31 11 ;

出版信息

Expert Opin Drug Saf. 2015;14(11):1661-71. doi: 10.1517/14740338.2015.1089231. Epub 2015 Oct 13.

Abstract

BACKGROUND

We conducted a meta-analysis to assess the overall risk of cardiac toxicity associated with trastuzumab treatment in elderly breast cancer patients.

METHODS

We searched databases from PubMed, EMBASE and Cochrane Central Registry of Controlled Trials to identify relevant studies. Statistical analyses were conducted to calculate the incidence rate, overall hazard ratio (HR) and 95% CIs using a fixed effects model.

RESULTS

A total of 116,342 and 360 elderly patients from five cohort studies and two randomized clinical trials (RCTs) were included for analysis. The pooled incidences of symptomatic congestive heart failure (CHF) and CHF/HF/CM were 6.4% (95% CI 4.1% - 9.4) and 16.4% (95% CI 16.19% - 16.61) in patients with median age of 67.5 years from two RCTs and in patients with median age of 67.5 (60 - 75), 71 (66 - 80+), 74.5 (65 - 89), 75 (66 - 81+) and 79.5 (60 - 99) from five cohort studies, respectively. Trastuzumab was significantly correlated with an increased risk of defined cardiac toxicities in five cohort studies (HR = 1.89, 95% CI 1.72 - 2.07, p < 0.00001) and two RCTs (HR = 3.00, 95% CI 1.71, 5.26, p < 0.00001). Sub-group analysis showed that the anthracycline-based chemotherapy increased the risk of CHF/HF and CM in patients among five cohort studies (HR = 2.16, 95% CI: 1.8 - 1.87, p < 0.00001).

CONCLUSION

Trastuzumab is likely associated with an increased risk of cardiac toxicity in elderly patients with HER-2-positive breast cancer. Carefully monitoring cardiac function in elderly patients receiving trastuzumab, particularly with concurrent use of anthracycline, is warranted.

摘要

背景

我们进行了一项荟萃分析,以评估老年乳腺癌患者接受曲妥珠单抗治疗时发生心脏毒性的总体风险。

方法

我们检索了PubMed、EMBASE和Cochrane对照试验中央注册库等数据库,以识别相关研究。采用固定效应模型进行统计分析,计算发病率、总体风险比(HR)和95%置信区间(CI)。

结果

五项队列研究和两项随机临床试验(RCT)共纳入116342例和360例老年患者进行分析。来自两项RCT的中位年龄为67.5岁的患者以及来自五项队列研究的中位年龄分别为67.5(60 - 75)、71(66 - 80+)、74.5(65 - 89)、75(66 - 81+)和79.5(60 - 99)岁的患者中,有症状性充血性心力衰竭(CHF)和CHF/HF/CM的合并发病率分别为6.4%(95%CI 4.1% - 9.4)和16.4%(95%CI 16.19% - 16.61)。在五项队列研究(HR = 1.89,95%CI 1.72 - 2.07,p < 0.00001)和两项RCT(HR = 3.00,95%CI 1.71,5.26,p < 0.00001)中,曲妥珠单抗与特定心脏毒性风险增加显著相关。亚组分析显示,在五项队列研究的患者中,基于蒽环类药物的化疗增加了CHF/HF和CM的风险(HR = 2.16,95%CI:1.8 - 1.87,p < 0.00001)。

结论

曲妥珠单抗可能与HER-2阳性老年乳腺癌患者心脏毒性风险增加有关。对于接受曲妥珠单抗治疗的老年患者,尤其是同时使用蒽环类药物的患者,有必要仔细监测其心脏功能。

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