Researchers investigating phase 2/3 clinical trials for cancer therapies found that 34% of trials studied excluded patients with cardiovascular disease from enrollment. These findings, published in Circulation, coupled with the prevalence of cardiovascular disease in patients with cancer, suggest that researchers should critically evaluate trial eligibility criteria and open up patient access to clinical trials for cancer treatment to better reflect real-world populations.
Overall, the researchers looked at 189 trials that included 97,556 patients and 123 US Food and Drug Administration-approved cancer treatments. While trials that were studying drug classes known to have cardiotoxicity reports (eg, immune checkpoint inhibitors) were more likely to exclude patients with cardiovascular toxicity (odds ratio, 3.09 [1.64-5.81]), this trend was also seen in trials that were studying treatments without previous reports of cardiovascular disease risk (eg, immunotherapies). One in 3 trials excluded patients with cardiovascular disease; more than 50% of trials studying breast cancer treatments excluded patients based on heart disease risk status.
Common exclusion criteria included heart failure (28%), coronary disease (27%), arrhythmias (23%), and recent myocardial infarction within 12 months (20%). Thirty-seven (58%) trials had multiple cardiovascular disease factors listed as exclusion criteria.
The researchers also noted that measures for cardiovascular disease exclusion were incongruous across trials that were evaluating treatments with known cardiotoxicity risk. “Many trials employed non-discrete or ill-defined reasons for the exclusion of CVD … with the availability of more objective and reliable CVD measures, inconsistent application of discrete criteria is inadequate,” Janice Bonsu, MPH, of the division of cardiology, Cardio-Oncology Program at The Ohio State University Medical Center in Columbus, and colleagues wrote.
Standardized cardiovascular disease definitions that may allow for more practical interpretation of drug safety were defined as left ventricular ejection fraction less than 50% for heart failure and blood pressure higher than 180/100 mmHg for hypertension.
Nearly 30% of patients who are diagnosed with cancer have concomitant cardiovascular disease, which is known to lead to poorer outcomes compared with cancer alone.
The authors warned that the lack of inclusion of patients with cardiovascular disease in cancer clinical trials may play a role in the inconsistency between rates of cardiovascular disease events reported in the trial setting compared with those seen in real-world patients, and encouraged the inclusion of patients with cardiovascular disease across cancer clinical trials, when feasible.
- Bonsu J, Charles L, Guha A, et al. Representation of patients with cardiovascular disease in pivotal cancer clinical trials. doi: 10.1161/CIRCULATIONAHA.118.039180