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 1 , Wuguo Tian 1 , Bo Gao 1 , Yan Jiang 1 , Xiaohua Zhang 1 , Shu Zhang 1 , Lingji Guo 1 , Jianjie Zhao 1 , Gang Zhang 1 , Chunyan Hu 1 , Jie Yan 1 , Donglin Luo 1 1 Department of Breast, Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China Correspondence to: Donglin Luo, email: donglinluo2016@21cn.com Keywords: dual Her-2 blockade, Her2, adverse events, breast cancer, meta-analysis Received: August 04, 2016      Accepted: October 19, 2016      Published: February 10, 2017 ABSTRACT 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.