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Dual HER-2 blockade therapy increases the risk of developing cardiac toxicities in HER-2 positive breast cancer: an up-to-date comprehensive meta-analysis
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  • wei-xiang Qi,
  • Lu Cao,
  • Cheng Xu ,
  • Shengguang Zhao,
  • Jiayi Chen
wei-xiang Qi
Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital
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Lu Cao
Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital
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Cheng Xu
Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital
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Shengguang Zhao
Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital
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Jiayi Chen
Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital
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Peer review status:UNDER REVIEW

23 Jun 2020Submitted to British Journal of Clinical Pharmacology
24 Jun 2020Assigned to Editor
24 Jun 2020Submission Checks Completed
26 Jun 2020Reviewer(s) Assigned

Abstract

Background To investigate the incidence and risk of cardiac toxicities between dual HER-2 blockade and anti-HER-2 monotherapy. Materials and methods We searched PubMed, EMBASE and Cochrane library databases to identify relevant trials between January 1 1990 and October 31 2019. Statistical analyses were conducted to calculate the summary incidence, Petro odds radio (Peto ORs) and 95% confidence intervals (CIs) by using either random-effects or fixed-effects models. Results A total of 16,375 patients from 15 randomized controlled trials were included for analysis; the pooled incidence of LVEF decline and CHF in dual HER-2 blocked were 4.6% and 0.9%, which was higher than that in anti-HER-2 monotherapy (3.2% and 0.7%, respectively). Dual HER-2 blockade therapy in breast cancer patients significantly increased the risk of developing LVEF decline (OR:1.19, 95%CI: 1.02-1.40, p=0.031) and CHF (OR:1.45, 95%CI: 1.00-2.11, p=0.049) when compared to anti-HER2 monotherapy. Sub-group analysis showed that addition of dual HER-2 blockade to adjuvant treatment for breast cancer significantly increased the risk of developing LVEF decline (p=0.048) and CHF (p=0.005). In addition, dual HER-2 blockade in breast cancer patients significantly increased the risk of developing LVEF decline (p=0.004) when compared to lapatinib alone, but not for CHF (p=0.11, respectively). Conclusion Dual HER-2 targeted therapy in HER-2 positive breast cancer significantly increase the risk of developing LVEF and CHF when compared to anti-HER-2 alone, though the overall incidence of cardiac toxicities is very low. Physicians should be aware of this risk and provide close monitoring during the administration of dual HER-2 targeted therapy.