Research Papers:

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

Shuai Hao, Wuguo Tian, Bo Gao, Yan Jiang, Xiaohua Zhang, Shu Zhang, Lingji Guo, Jianjie Zhao, Gang Zhang, Chunyan Hu, Jie Yan and Donglin Luo _

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Oncotarget. 2017; 8:19923-19933. https://doi.org/10.18632/oncotarget.15252

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Shuai Hao1, Wuguo Tian1, Bo Gao1, Yan Jiang1, Xiaohua Zhang1, Shu Zhang1, Lingji Guo1, Jianjie Zhao1, Gang Zhang1, Chunyan Hu1, Jie Yan1, Donglin Luo1

1Department of Breast, Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China

Correspondence to:

Donglin Luo, email: [email protected]

Keywords: dual Her-2 blockade, Her2, adverse events, breast cancer, meta-analysis

Received: August 04, 2016     Accepted: October 19, 2016     Published: February 10, 2017


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.

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