TY - JOUR
T1 - REPRESENTATION OF CARDIOVASCULAR DISEASE PATIENTS IN PIVOTAL CLINICAL TRIALS SUPPORTING MODERN CANCER THERAPIES
AU - Addison, Daniel
AU - Bonsu, Janice
AU - Charles, Lawrence
AU - Guha, Avirup
AU - Awan, Farrukh
AU - Jneid, Hani
AU - Woyach, Jennifer
PY - 2019/3
Y1 - 2019/3
N2 - Background: Cardiovascular disease (CVD) is common among new cancer patients. Cancer patients with concurrent CVD have poorer outcomes. Despite the high prevalence of CVD and its prognostic significance, there is limited evidence to guide CVD care and monitoring during cancer treatment. Clinical trials of new anticancer drugs are reviewed by the Food and Drug Administration (FDA) for adequate representation prior to drug approval. Yet, whether CVD patients are adequately represented is unknown. Methods: From the Drugs@FDA database and FDA reviews, we identified all anticancer drug approvals from 1998-2018. Latter phase (II and III) clinical trials tied to drug approvals were identified through MEDLINE, clinicaltrial.gov, and publically available FDA drug reviews. The inclusion of patients with baseline CVD, defined as hypertension, coronary disease, heart failure (HF), arrhythmia, thromboembolic disease, stroke, abnormal ECG, or any mention of CVD was examined. Multivariable logistic regression was used to assess for trial characteristics, including cancer type, drug class, trial size, funding source, trial phase, prior in class cardiotoxicity, and observed early phase (safety) trial CVD, were associated with CVD exclusion. We also assessed for differences in drug efficacy using pooled binary and continuous endpoint hazard ratios (HR), respectively, based on the inclusion or exclusion of CVD patients. Results: In total, 189 clinical trials, evaluating 97,365 participants (58.5±5 years, 46.0% female, 80.4% on biologic, targeted or immune-therapies), supporting 123 FDA approved drugs were identified, of which 34% excluded patients with CVD. HF was the most common reason for exclusion (28%). Trials evaluating drugs within classes with prior cardiotoxicity reports (ex. immune checkpoint inhibitors), were more likely to exclude CVD. In a multivariable model, no other measured trial characteristics, including the presence or absence of early phase reports of excess-risk, were associated with CVD exclusion. There was no difference in drug efficacy based on CVD exclusion. Conclusion: CVD patients were frequently excluded from pivotal clinical trials tied to modern cancer therapies.
AB - Background: Cardiovascular disease (CVD) is common among new cancer patients. Cancer patients with concurrent CVD have poorer outcomes. Despite the high prevalence of CVD and its prognostic significance, there is limited evidence to guide CVD care and monitoring during cancer treatment. Clinical trials of new anticancer drugs are reviewed by the Food and Drug Administration (FDA) for adequate representation prior to drug approval. Yet, whether CVD patients are adequately represented is unknown. Methods: From the Drugs@FDA database and FDA reviews, we identified all anticancer drug approvals from 1998-2018. Latter phase (II and III) clinical trials tied to drug approvals were identified through MEDLINE, clinicaltrial.gov, and publically available FDA drug reviews. The inclusion of patients with baseline CVD, defined as hypertension, coronary disease, heart failure (HF), arrhythmia, thromboembolic disease, stroke, abnormal ECG, or any mention of CVD was examined. Multivariable logistic regression was used to assess for trial characteristics, including cancer type, drug class, trial size, funding source, trial phase, prior in class cardiotoxicity, and observed early phase (safety) trial CVD, were associated with CVD exclusion. We also assessed for differences in drug efficacy using pooled binary and continuous endpoint hazard ratios (HR), respectively, based on the inclusion or exclusion of CVD patients. Results: In total, 189 clinical trials, evaluating 97,365 participants (58.5±5 years, 46.0% female, 80.4% on biologic, targeted or immune-therapies), supporting 123 FDA approved drugs were identified, of which 34% excluded patients with CVD. HF was the most common reason for exclusion (28%). Trials evaluating drugs within classes with prior cardiotoxicity reports (ex. immune checkpoint inhibitors), were more likely to exclude CVD. In a multivariable model, no other measured trial characteristics, including the presence or absence of early phase reports of excess-risk, were associated with CVD exclusion. There was no difference in drug efficacy based on CVD exclusion. Conclusion: CVD patients were frequently excluded from pivotal clinical trials tied to modern cancer therapies.
UR - https://www.mendeley.com/catalogue/f856db5b-8ce6-3ce4-bec3-193cb41a9033/
U2 - 10.1016/s0735-1097(19)32483-0
DO - 10.1016/s0735-1097(19)32483-0
M3 - Article
SN - 0735-1097
VL - 73
SP - 1877
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 9
ER -