In a study reported in JACC:CardioOncology, Rankin et al analyzed the degree to which published phase II to IV trials of combination immune checkpoint inhibitor (ICI) and VEGF inhibitor treatment for cancer reported cardiovascular eligibility criteria and adverse events.
As stated by the investigators: “Combination therapy with ICIs and VEGF inhibitors has improved cancer outcomes and is increasingly used. These drug classes are associated with cardiovascular toxicities when used alone, but heterogeneity in trial design and reporting may limit knowledge of toxicities in patients receiving these in combination.”
Study Details
In a search for published phase II to IV randomized controlled trials of ICI plus VEGF inhibitor therapy for solid tumors, 17 trials with a population of 10,313 patients reported between 2018 and 2022 were identified.
Key Findings
Multiple cardiovascular exclusion criteria were specified in 15 of 17 trials. Among these trials, 13 listed specific exclusion criteria for prior heart failure, myocardial infarction or unstable angina, and stroke. Patients with reduced left ventricular ejection fraction were excluded from eight trials.
In 12 trials reporting cardiovascular eligibility criteria prior to enrollment, 31% of recruited patients were ineligible for the trials.
Baseline prevalence of cardiovascular disease, including cardiovascular risk factors or established cardiovascular disease, was not reported in any of 16 primary trial publications. A secondary analysis of one trial reported baseline cardiovascular risk factors.
Among the studies, there was considerable heterogeneity in defining cardiovascular conditions. Grade 1 to 4 cardiovascular adverse events were reported when the incidence was between 5% and 25% in 15 trials. Incident hypertension was recorded in all trials, but there was no consistent recording of other cardiovascular events. No trial specifically noted the absence of cardiovascular events.
The investigators concluded: “In ICI and VEGF inhibitor combination trials, there is heterogeneity in cardiovascular exclusion criteria, reporting of baseline characteristics, and reporting of cardiovascular adverse events. This limits an optimal understanding of the incidence and severity of events relating to these combinations. Better standardization of these elements should be pursued.”
Ninian N. Lang, PhD, FRCP, of the BHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow, the corresponding author of the JACC:CardioOncology article.
Disclosure: For full disclosures of the study authors, visit jacc.org.
