Cardiovascular (CV) endpoints in oncology trials should be selected according to the expected mechanism of toxicity, new international guidance advises.
The scientific statement from the American Heart Association (AHA) provides a framework for selecting and assessing validated CV endpoint definitions to better standardise safety and efficacy monitoring in oncology trials.
It also emphasises the importance of patient-reported outcomes (PROs) and long-term follow-up of CV endpoints in clinical trials, while suggesting that composite and surrogate endpoints should be clearly defined and only used as secondary or exploratory endpoints.
“By harmonising cardiovascular endpoint assessment across oncology trials, this scientific statement aims to enhance risk stratification, facilitate regulatory acceptance, and inform clinical decision-making, ultimately improving patient safety while supporting innovation in cancer therapeutics,” wrote the authors, led by Professor Ana Barac, Professor of Medicine at Georgetown University, Washington DC, US.
The scientific statement, published in the Journal of Clinical Oncology [link here], first outlines the various mechanisms by which cancer therapies can impact the cardiovascular system.
The authors propose a framework for selecting endpoints, with routine clinical data recommended for early-phase trials, but endpoints and monitoring methods determined by the expected mechanism of CV toxicity in later-phase trials.
For example, if atherosclerosis is expected, endpoints could include myocardial infarction/revascularisation, ischaemic stroke and acute limb ischaemia, measured through imaging and biomarkers if appropriate.
“The choice of relevant cardiovascular endpoints incorporates contemporary, standardised, and validated definitions—such as those provided by professional societies and regulatory agencies—that are applied to ensure consistency, reproducibility, and comparability across studies,” the statement notes.
Validated surrogate endpoints, such as left ventricular ejection fraction and QT prolongation, should only be used if they have been shown to predict clinical benefits or risks of MACE.
Composite endpoints, such as CV disease–free survival, should be secondary or exploratory as combining efficacy and safety outcomes can complicate interpretation of the benefit–risk profile, meaning they have limited utility for regulatory decisions.
Similarly, the statement notes the “major opportunities” offered by remote, decentralised or hybrid clinical trials, suggesting that digital CV biomarkers can be used as exploratory or secondary endpoints if they are clearly defined.
The authors also give guidance on baseline CV assessments that should be carried out and routine assessments during the trial, while calling for improved monitoring in long-term follow-up of trials.
“With improving survivorship across many adult cancer diagnoses, the consideration of long-term cardiovascular outcomes becomes imperative,” they note.
“Contemporary oncology trials should prioritise consensus-driven, validated cardiovascular endpoints; incorporate adjudication processes; and adopt risk-based approaches within trial design,” they conclude.
“Enhanced collaboration between oncology and cardiology, along with transparent reporting and stakeholder alignment on the value of cardiovascular endpoints, will be key to advancing both the safety and efficacy of novel cancer therapies,” they add.