Introduction: The introduction of targeted cancer therapies has contributed to dramatic improvements in patient survival. Nevertheless, several of these therapies have been associated with adverse effects, including cardiovascular toxicity. These concerns are based on varying levels of evidence that has not been synthesised systematically to-date. We therefore assessed published systematic review evidence of cardiovascular toxicity associated with targeted cancer therapies.
Methods and analysis: We included systematic reviews of randomised controlled trials and observational studies that reported on cardiovascular outcomes for individual agents published to the end of 2016. Systematic reviews including head-to-head comparisons were excluded. We identified systematic reviews by applying an a priori, standardised search strategy executed across multiple databases. We extracted and reported data according to published methodological guidelines, and incorporated quality assessment. Our narrative synthesis involved classification of agents based on systematic review evidence of toxicity (sufficient, probable, possible, or indeterminate) for specific cardiovascular outcomes including: cardiac events (left ventricular toxicity, myocardial infarction, ischaemic heart disease, QT prolongation, unspecified cardiac events), thromboembolic events (cerebrovascular events, venous thromboembolism, arterial thromboembolism), and hypertension.
Results: Of 11,942 citations identified, 101 met study inclusion criteria and contributed to our narrative synthesis. There were 16 agents with sufficient or probable systematic review evidence of cardiovascular toxicity, including: cardiac events (abiraterone, pazopanib, vandetanib, bevacizumab, trastuzumab), thromboembolic events (tamoxifen, sorafenib, bevacizumab, cetuximab, panitumumab, lenalidomide, thalidomide), and hypertension (abiraterone, axitinib, cediranib, pazopanib, regorafenib, sorafenib, vandetanib, bevacizumab, ramucirumab, aflibercept).
Conclusions: Treatment-induced cardiovascular toxicity is of increasing concern in oncology, and the literature is vast. This study identified 16 agents with sufficient or probable systematic review evidence of cardiovascular toxicity and provides an accessible synthesis based on robust, best-practice methodology. Our study is limited by restriction to systematic reviews, which may exclude newer agents, reflect healthier populations and involve shorter follow up times compared to real-world practice.