How do breast cancer clinical trials approach cardiovascular safety: targeted or generalized?

Abstract

Background: Different breast cancer pharmacotherapy agents cause different forms of cardiovascular toxicity. We aim to assess if breast cancer pharmacotherapy trials approach cardiovascular safety in a targeted or generalized manner when administering different agents.

Methods: We searched Embase and Medline for phase 2 and 3 breast cancer pharmacotherapy trials. We examined exclusion criterion for cardiovascular conditions and cardiovascular safety assessment through cardiovascular imaging, electrocardiogram, troponin, or natriuretic peptides. Fisher's exact test was utilized to compare reporting.

Results: Fifty breast cancer clinical trials were included in this study. Trials administering microtubule inhibitors were most likely to exclude patients with any CV condition compared with trials administering other agents (93.5% vs. 68.4%; p < 0.05), particularly coronary artery disease (77.4% vs. 36.8%; p < 0.01) but reported performing an electrocardiogram in 13 (41.9%) trials. Trials administering anti-HER 2 agents excluded all patients with at least one CV condition, particularly patients with heart failure (100.0% vs. 62.9%) and were more likely to perform echocardiograms (80.0% vs. 22.9%, p < 0.001) compared with other agents. Other agents excluded participants in a generalized manner and do not frequently perform targeted safety assessments.

Conclusions: Only trials administering microtubule inhibitors or anti-HER 2 therapy exclude patients with cardiovascular disease in a targeted approach. However, anti-HER 2 therapy trials are the only breast cancer clinical trials that perform targeted safety assessments. Breast cancer clinical trials need to develop a targeted approach to cardiovascular safety assessments to permit inclusion of high-risk participants and generate clinical trial data generalizable to patients with cardiovascular disease undergoing cancer therapy.