Adverse cardiovascular events associated with kinase inhibitors and the prognostic value of imaging – a single-center retrospective cohort study in cancer patients
J Singh, J Cross, Y Im, U Siddiqi, L Baldassarre, J M KwanAbstract
Background/Introduction
Kinase inhibitors (KIs) represent the largest class of targeted small molecule agents and have revolutionized the landscape of cancer therapies [1]. However, certain agents have generated safety concerns due to reported cardiotoxicities [2]. Hypothesized mechanisms of cardiotoxicity vary depending on the agent and is thought to be a consequence of inherent non-selectivity and the multi-targeted nature of KIs [3]. Given that KIs are a cornerstone in cancer therapy, it is pivotal to understand its association with potential cardiovascular toxicities. Many of the prior studies were limited by small cohort size and were primarily focused on select subsets of KI agents.
Purpose
We analyzed adverse cardiovascular events (ACE) and the prognostic value of imaging in a large cohort of cancer patients treated with a broad spectrum of KI agents with the goal of guiding further investigation and informing clinical decision-making.
Methods
We performed a single-center retrospective cohort analysis of cancer patients treated with KIs from 2013 to 2024. The primary outcome was post-KI ACE (myocardial infarction (MI), coronary artery disease (CAD), stroke, peripheral vascular disease, heart failure (HF), valvular disease, and pericardial disease). Cox regression with competing risks identified covariates, and imaging associations with outcomes were evaluated.
Results
Of the 1,897 patients in our cohort, those who experienced post-KI ACE were older, had higher BMI, and had worse pre-existing cardiovascular disease (CVD) burden and comorbid conditions (Figure 1A). Regorafenib and sorafenib use were independently associated with increased ACE risk. (Figure 1B). Among patients with echocardiograms, 52% pre-KI and 46.9% post-KI had abnormal strain, a measure reflective of left ventricular dysfunction. Abnormal strain pre-KI was associated with developing arrhythmia, HF, and CAD/MI (Figure 1C). A left ventricular ejection fraction (LVEF) <55% by echo was present in 23% pre-KI. Those with abnormal vs normal pre-KI LVEF were more likely to have a drop in LVEF by >10% (43.5% vs 10.9%, p <0.001).
Conclusions
Patients with prior CVD had significantly increased risk of ACE with KI therapy, with the agents regorafenib and sorafenib being independently associated with increased ACE risk. In cancer patients receiving KIs, optimization of cardiac risk factors should be a priority. Our findings support the 2022 European Society of Cardiology (ESC) guideline recommendations for baseline imaging, given the high proportion of patients with abnormal echo prior to KI treatment and its prognostic value for CV outcomes.Figure