Cardiovascular Safety Reporting in Contemporary Breast Cancer Clinical Trials

Abstract

Background Several cancer therapies have been associated with cardiovascular harm in early‐phase clinical trials. However, some cardiovascular harms do not manifest until later‐phase trials. To limit interdisease variability, we focused on breast cancer. Thus, we assessed the reporting of cardiovascular safety monitoring and outcomes in phase 2 and 3 contemporary breast cancer clinical trials. Methods and Results We searched Embase and Medline records for phase 2 and 3 breast cancer pharmacotherapy trials. We examined exclusion criterion as a result of cardiovascular conditions, adverse cardiovascular event reporting, and cardiovascular safety assessment through cardiovascular imaging, ECG, troponin, or natriuretic peptides. Fisher's exact test was utilized to compare reporting. Fifty clinical trials were included in our study. Patients were excluded because of cardiovascular conditions in 42 (84%) trials. Heart failure was a frequent exclusion criterion (n=31; 62% trials). Adverse cardiovascular events were reported in 43 (86%) trials. Cardiovascular safety assessments were not reported in 23 (46%) trials, whereas natriuretic peptide and troponin assessments were not reported in any trial. Cardiovascular safety assessments were more frequently reported in industry‐funded trials (69.2% versus 0.0%; P <0.001), and in trials administering targeted/immunotherapy agents compared with only hormonal/conventional chemotherapy (78.6% versus 22.7%, P <0.001). Conclusions Our findings demonstrate significant under‐representation of patients with cardiovascular conditions or prevalent cardiovascular disease in contemporary later‐phase breast cancer trials. Additionally, cardiovascular safety is not routinely monitored in these trials. Therefore, contemporary breast cancer clinical trials may possibly underestimate the cardiovascular risks of cancer pharmacotherapy agents for use in clinical practice.