Abstract 14765: Cardiovascular Safety Reporting Among Cancer Pharmacotherapy Agents in Breast Cancer Clinical Trials

Abstract

Introduction: Cancer pharmacotherapy has been associated with cardiovascular (CV) harm in early phase trials. Later phase (2 & 3) trials offer potential to uncover the frequency of CV harm not identified in smaller early phase trials. We assessed whether the cancer pharmacotherapy agent administered impacts how later phase breast cancer clinical trials exclude patients and report CV safety assessments. Methods: We searched Embase and Medline records for phase 2 & 3 breast cancer pharmacotherapy trials (2018-2019). We examined exclusion criteria due to CV conditions and CV safety assessment through CV imaging, electrocardiograms, or biomarkers. Fischer’s exact test was utilized to compare reporting. Results: After our search, 50 clinical trials were included. Trials administering microtubule inhibitors were most likely to exclude participants with CV conditions (e.g. myocardial infarctions and arrhythmias) compared to other agents (kinase inhibitors etc.) (93.5 vs 68.4%, p=0.04). Trials administering HER-2 receptor antibody agents more often excluded patients with heart failure (HF) or low ejection fraction (EF) compared to other agents (100.0 vs 62.9%, p<0.01). Trials administering anthracyclines frequently exclude patients with HF or low EF, albeit not statistically more than other agents (92.9 vs 66.7%, p=0.07). Only 46% trials performed electrocardiograms, 40% performed CV imaging, and none reported biomarker collection. Trials administering HER-2 receptor antibody agents conducted the greatest CV imaging (p<0.01). While trials utilizing other agents did not selectively perform relevant safety assessments to identify toxicity the agent would be at risk of inducing compared to all agents. Conclusion: HER-2 receptor antibody trials selectively exclude patients with at risk conditions and conduct imaging to monitor cardiotoxicity. However, breast cancer trials using other pharmacotherapies do not have a uniform approach to CV exclusion criteria or safety assessments. Breast cancer pharmacotherapy trials should establish a standardized approach to conduct safety assessments that can identify early CV toxicity specific to the agent administered. This may allow inclusion of high risk patients and generate more generalizable data.