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中国学者发现HER2双阻断不增加乳腺癌患者严重毒性风险

2021-08-05 14:39:04


  尽管HER2双阻断治疗可以为乳腺癌提供更好的临床效果,但是与乳腺癌联合方案相关的严重毒性风险仍然未知。


  2017年2月10日,美国《肿瘤标靶》在线发表重庆大坪医院(第三军医大学第三附属医院)的随机对照研究荟萃分析,发现HER2双阻断治疗并不增加乳腺癌患者严重毒性风险。


  该研究系统检索了公共数据库(MEDLINE、EMBASE、Cochrane文献库)以确定比较抗HER2单药疗法(拉帕替尼或曲妥珠单抗或帕妥珠单抗)与HER2双阻断治疗(帕妥珠单抗+曲妥珠单抗或曲妥珠单抗+拉帕替尼)乳腺癌的相关研究,筛选出9项研究共11941例乳腺癌患者。


  荟萃分析显示,HER2双阻断治疗的严重腹泻、治疗中止的风险分别显著增加2.52、1.52倍(P<0.001、=0.014),严重皮疹、肝脏毒性、充血性心力衰竭、左心室射血分数(LVEF)下降、致命不良事件的风险无统计学显著差异(比值比:1.06、1.16、1.46、1.09、0.97,P=0.81、0.28、0.09、0.40、0.91)。在根据抗HER2方案的亚组分析中,严重腹泻、治疗中止的风险结果相似。此外,曲妥珠单抗+拉帕替尼与拉帕替尼单药相比,LVEF下降风险显著增加1.48倍(P=0.002)。


  该分析结果表明,抗HER2双阻断治疗与抗HER2单药治疗相比,显著增加严重腹泻和治疗中止的风险,无证据表明HER2双阻断治疗的致命不良事件风险增加。


Oncotarget. 2017 Feb 10. [Epub ahead of print]


Does dual HER-2 blockade treatment increase the risk of severe toxicities of special interests in breast cancer patients: A meta-analysis of randomized controlled trials.


Hao S, Tian W, Gao B, Jiang Y, Zhang X, Zhang S, Guo L, Zhao J, Zhang G, Hu C, Yan J, Luo D.


Department of Breast, Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.


Although dual HER-2 blockade treatment could offer greater clinical efficacy in breast cancer, the risk of severe toxicities of special interest related to this combined regimen in breast cancer remained unknown. We systematically searched public databases (MEDLINE, EMBASE, Cochrane library) to identify relevant studies that comparing anti-HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) with dual HER-2 blockade treatment (pertuzumab plus trastuzumab or trastuzumab plus lapatinib) in breast cancer. A total of 11,941 breast cancer patients from 9 trials were included for analysis. Meta-analysis showed that dual HER2 blockade treatment significantly increased the risk of severe diarrhea (OR 2.52, p<0.001) and treatment discontinuation (OR 1.52, p=0.014), but not for severe rash (OR 1.06, p=0.81), liver toxicities (OR 1.16, p=0.28), CHF (OR 1.46, p=0.09), LVEF decline (OR 1.09, p=0.40) and FAEs (OR 0.97, p=0.91). Similar results were observed in sub-group analysis according to anti-HER2 regimens in terms of severe diarrhea and treatment discontinuation. Additionally, trastuzumab plus lapatinib significantly increased the risk of LVEF decline in comparison with lapatinib alone (OR 1.48, p=0.002). Our analysis indicated that dual anti-HER2 blockade treatment significantly increased the risk of developing severe diarrhea and treatment discontinuation in comparison with anti-HER2 monotherapy. These were no evidence of an increased risk of fatal adverse events with dual-HER2 blockade treatment.


KEYWORDS: Her2; adverse events; breast cancer; dual Her-2 blockade; meta-analysis


PMID: 28199966


DOI: 10.18632/oncotarget.15252













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