Cardiotoxicity of HER-2-targeted drugs when combined with other drugs: A systematic review and single-rate meta-analysis

Objective: To assess the incidence of cardiovascular adverse events when HER-2-targeted drugs were combined with other drugs. Methods: : We looked through the literature on the cardiotoxicity of anti-HER-2 drugs in electronic databases, including PubMed, Web of Science, Cochrane Library, OVID and CNKI, from their inception to April 2022. The Cochrane Collaboration’s tool for assessing risk of bias and the Jadad scale were used to evaluate the risk of bias and quality of the studies, respectively. The meta-analysis was performed using R 4.2.1. Outcomes: We included 41 randomized clinical trials (RCTs) in the meta-analysis, consisting of 56 groups and 31,934 patients. The meta-analysis revealed the following: 1) The incidence of cardiotoxicity in groups given monoclonal antibody treatment was 10%-14%, while in groups given antibody‒drug conjugates (ADC), it was 1%-5%, a significant difference (P<0.01). 2) When monoclonal antibodies were combined with chemotherapy, the incidence of cardiotoxicity under anthracycline-containing therapy (10.3%) was significantly higher than that under non-anthracycline-containing therapy (8.8%). 3) Significant differences were found between subgroups except the endocrine group and others, though this kind of difference might result from the different inclusion criteria of the original trials. Conclusion: 1) When anti-HER-2 drugs are given together with anthracycline-containing chemotherapy, the incidence of cardiotoxicity is obviously higher than with other drugs. 2) Safety rewards could be gained if traditional monoclonal antibodies are replaced by ADCs. The detailed use of drugs requires joint efforts by oncologists and cardiologists.