Cardiotoxicity prevention trials in the era of contemporary cancer therapies: a systematic review

Cardiovascular toxicity is an increasingly important limitation of effective contemporary cancer therapies. Yet, the extent to which trials focus on preventing cardiotoxic events in patients receiving contemporary therapies is unknown. Leveraging PubMed, CENTRAL, clinicaltrials.gov, and publicly available reviews to identify all randomized controlled trials (RCTs) testing interventions for prevention or management of cardiotoxicity in cancer patients through 2024, we assessed the proportion of cardiotoxicity prevention trials that studied contemporary cancer therapies (biologic, targeted, or immune-based therapies). We included RCTs of interventional therapies/strategies against cardiotoxicity during cancer treatment. Data on trial baseline characteristics, design, funding, and reporting were extracted. Regression models were used to define trial and population factors associated with drug selection, reporting bias, and subsequent translation into guidelines. Overall, there were 126 trials, evaluating 15 prevention strategies, enrolling 16,111 participants (45.6 ± 13.9 years, 81.3% female, median trial duration of 23 months). Among trials, 17.5% evaluated patients receiving biologic, targeted, and/or immune-based therapies, including 2.4% of trials focused on immune-based therapies (one IL-2 and two immune checkpoint inhibitors). Most trials (109 [86.5%]) used surrogate endpoints. Over time, there was no temporal increase in the proportion of trials assessing biologic, targeted, or immune-based cancer therapies. Collectively, these data suggest that among trials focused on preventing cardiotoxicity, contemporary cancer therapies were not frequently evaluated. • Among 126 cardiotoxicity prevention trials, < 1 in 5 assessed contemporary cancer therapies and <5% assessed immune-based therapies. •Most cardiotoxicity focused trials suffered from significant limitations including reliance on surrogate endpoints raising an unmet need.