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Cardiac toxicities of lapatinib in patients with breast cancer and other HER2-positive cancers: a meta-analysis

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Abstract

Purpose

Lapatinib is a tyrosine kinase inhibitor that targets the human epidermal growth factor receptor 2 (HER2) and the epidermal growth factor receptor (EGFR/HER1), and there are concerns about its cardiac toxicity. Recent studies of lapatinib have reported cardiac adverse events; however, the results have been inconsistent among the studies. The aim of our study was to estimate the cardiac toxicity of lapatinib in patients with breast cancer and other HER2-positive cancers.

Methods

To evaluate the cardiotoxicity of lapatinib, the results of previous studies were quantitatively integrated using meta-analysis. Forty-five articles regarding cardiac adverse events, including left ventricular dysfunction, left ventricular ejection fraction (LVEF) decrease, arrhythmia, and other cardiac adverse events, were assessed. As a subgroup analysis in patients with breast cancer, 26 studies of lapatinib-induced cardiac adverse events were assessed.

Results

The overall incidence of cardiac adverse events was 2.70% (95% confidence interval [CI] 1.60–4.50%). The incidences of left ventricular dysfunction and LVEF decrease were 1.60% (95% CI 1.30–2.00%) and 2.20% (95% CI 1.30–3.60%), respectively. The overall incidence of cardiac adverse events was 3.00% (95% CI 1.50–6.10%) in patients with breast cancer, which was marginally higher than the rate in patients with all type of cancers.

Conclusion

The overall incidence of lapatinib-induced cardiac toxicity was relatively low based on an indirect comparison with trastuzumab. However, careful monitoring of cardiac toxicity is still needed when patients are treated with lapatinib because the related risk factors have not been clearly identified.

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Acknowledgements

This research was supported by the 2016 Yeungnam University Research Grant, and by Basic Science Research Program through the National Research Foundation of Korea (NRF) founded by the Ministry of Science, ICT and Future Planning (2017R1C1B5017085). We thank Prof. Kwang-Hee Shin for the help in statistical analysis.

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  1. College of Pharmacy, Yeungnam University, 280 Daehak-ro, Gyeongsan, Gyeongsangbuk-do, 38541, Republic of Korea

    Hye Duck Choi

  2. College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea

    Min Jung Chang

  3. Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, Republic of Korea

    Min Jung Chang

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Correspondence to Hye Duck Choi.

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Choi, H.D., Chang, M.J. Cardiac toxicities of lapatinib in patients with breast cancer and other HER2-positive cancers: a meta-analysis. Breast Cancer Res Treat 166, 927–936 (2017). https://doi.org/10.1007/s10549-017-4460-9

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