Predicting cardiovascular toxicity of targeted cancer therapy

Josh Mitchell, M.D., FACC

Project Summary:

Improvements in cancer treatment have helped lead to a significant increase in cancer survivors, currently numbering over 16 million in the U.S. Unfortunately, these survivors are at substantially increased risk for cardiovascular disease due to short- and long-term effects of their cancer treatment and a high prevalence of traditional cardiac risk factors. In some cancer populations, cardiovascular (CV) events have a greater impact on morbidity and mortality than the cancer itself. In others, it is the second leading cause of mortality behind the malignancy.

Confounding the problem, a significant lag can often exist between the release of a new cancer treatment and our understanding of its CV impact. Prior research has shown that CV events are insufficiently characterized in the original clinical trials, and the real-world population exposed to the cancer therapy often has a higher rate of baseline CV disease than the trial population, leading to increased cardiotoxicity. There is a tremendous need for research to better understand the cardiotoxic effects of cancer treatments in real-world patients, how to identify patients most at risk for cardiotoxicity, and ultimately, what modifications to regimens or cardioprotective medications have the most impact in improving morbidity and mortality. Using patient databases from the Department of Veterans Affairs, this project aims to extensively characterize the incidence and prevalence of CV disease and its impact on patient treatment and survival in patients that have been treated with three more recent cancer treatment regimens: checkpoint inhibitors; proteasome inhibitors; and tyrosine kinase inhibitors that target vascular endothelial growth factor (VEGF).