Cardiac Outcomes of Patients Receiving Adjuvant Weekly Paclitaxel and Trastuzumab for Node-Negative, ERBB2-Positive Breast Cancer
Cardiac Outcomes of Patients Receiving Adjuvant Weekly Paclitaxel and Trastuzumab for Node-Negative, ERBB2-Positive Breast Cancer
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DOI：
10.1001/jamaoncol.2015.3709
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发表时间：
2016-01-01
期刊：
影响因子：
28.4
通讯作者：
Tolaney, Sara M.
中科院分区：
文献类型：
--
作者：
Dang, Chau;Guo, Hao;Tolaney, Sara M.
重要性曲妥珠单抗是一种挽救生命的治疗，但与症状性和无症状性左心室射血分数（LVEF）下降相关。我们报告了以非蒽环类抗生素和曲妥珠单抗为基础的治疗对早期人类表皮生长因子受体2患者的心脏毒性作用ERBB 2（以前称为HER2或HER2/neu）阳性乳腺癌。目的确定紫杉醇联合曲妥珠单抗的心脏安全性以及LVEF监测在淋巴结阴性、ERBB 2阳性乳腺癌患者中的实用性。在这项对14个医学中心的非对照、单组研究的二次分析中，从2007年10月9日至9月3日，招募了406例淋巴结阴性、ERBB 2阳性乳腺癌3 cm或更小、基线LVEF大于或等于50%的患者，2010.淋巴结微转移的患者随后允许进行研究修订。患者年龄中位数为55岁，118例（29%）患有高血压，30例（7%）患有糖尿病。患者接受紫杉醇辅助治疗12周，曲妥珠单抗持续治疗1年。干预治疗包括每周80 mg/m2剂量紫杉醇同时静脉注射曲妥珠单抗12周，随后曲妥珠单抗单药治疗39周。在单药治疗阶段，曲妥珠单抗可以每周2 mg/kg或每3周一次6 mg/kg给药。在完成12周的化疗后，按照标准指南进行放射和激素治疗。在基线、12周、6个月和1年时评估患者的LVEF。主要结果和指标报告了心脏安全性数据，包括3至4级左心室收缩功能障碍（LVSD）和显著的无症状LVEF下降（根据我们的研究定义）。（0.5%）（95% CI，0.1%-1.8%）发生3级LVSD并退出研究，13例（3.2%）（95% CI，1.9%-5.4%）发生显著无症状LVEF下降，其中11例完成研究治疗。基线时的中位LVEF为65%; 12周时为64%; 6个月时为64%; 1年时为64%。结论和相关性紫杉醇联合曲妥珠单抗的心脏毒性作用，表现为3级或4级LVSD或无症状LVEF下降，较低。在基线、12周、6个月和1年时评估患者的LVEF，我们的研究结果表明，对于许多人来说，在曲妥珠单抗治疗期间不使用蒽环类药物的LVEF监测可以简化。
IMPORTANCE Trastuzumab is a life-saving therapy but is associated with symptomatic and asymptomatic left ventricular ejection fraction (LVEF) decline. We report the cardiac toxic effects of a nonanthracycline and trastuzumab-based treatment for patients with early-stage human epidermal growth factor receptor 2 (ERBB2, formerly HER2 or HER2/neu)-positive breast cancer.OBJECTIVE To determine the cardiac safety of paclitaxel with trastuzumab and the utility of LVEF monitoring in patients with node-negative, ERBB2-positive breast cancer.DESIGN, SETTING, AND PARTICIPANTS In this secondary analysis of an uncontrolled, single group study across 14 medical centers, enrollment of 406 patients with node-negative, ERBB2-positive breast cancer 3 cm, or smaller, and baseline LVEF of greater than or equal to 50% occurred from October 9, 2007, to September 3, 2010. Patients with a micrometastasis in a lymph node were later allowed with a study amendment. Median patient age was 55 years, 118 (29%) had hypertension, and 30 (7%) had diabetes. Patients received adjuvant paclitaxel for 12 weeks with trastuzumab, and trastuzumab was continued for 1 year. Median follow-up was 4 years.INTERVENTIONS Treatment consisted of weekly 80-mg/m(2) doses of paclitaxel administered concurrently with trastuzumab intravenously for 12 weeks, followed by trastuzumab monotherapy for 39 weeks. During the monotherapy phase, trastuzumab could be administered weekly 2-mg/kg or every 3 weeks as 6-mg/kg. Radiation and hormone therapy were administered per standard guidelines after completion of the 12 weeks of chemotherapy. Patient LVEF was assessed at baseline, 12 weeks, 6 months, and 1 year.MAIN OUTCOMES AND MEASURES Cardiac safety data, including grade 3 to 4 left ventricular systolic dysfunction (LVSD) and significant asymptomatic LVEF decline, as defined by our study, were reported.RESULTS Overall, 2 patients (0.5%) (95% CI, 0.1%-1.8%) developed grade 3 LVSD and came off study, and 13 (3.2%) (95% CI, 1.9%-5.4%) had significant asymptomatic LVEF decline, 11 of whom completed study treatment. Median LVEF at baseline was 65%; 12 weeks, 64%; 6 months, 64%; and 1 year, 64%.CONCLUSIONS AND RELEVANCE Cardiac toxic effects from paclitaxel with trastuzumab, manifesting as grade 3 or 4 LVSD or asymptomatic LVEF decline, were low. Patient LVEF was assessed at baseline, 12 weeks, 6 months, and 1 year, and our findings suggest that LVEF monitoring during trastuzumab therapy without anthracyclines could be simplified for many individuals.