https://orcid.org/0000-0002-3103-9739
Abstract
Therapeutic advancements have significantly enhanced cancer patient survival rates, yet concomitantly increased the prevalence of associated toxicities, such as cancer therapy-related cardiac dysfunction (CTRCD), either symptomatic (heart failure) or not. Using the World Health Organization’s VigiBase® individual case safety report database, the aim was to establish the association between anticancer drugs and CTRCD reporting.
This study was a disproportionality analysis conducted in VigiBase® from the initial report of any anticancer drug until February 29, 2024. Reporting odds ratios for CTRCD were evaluated using a stepwise selection procedure and multivariable-adjusted analyses. Subsequently, secondary analyses consisted of the decription of CTRCD cases associated with the identified anticancer drugs. Clinicaltrials.gov registration number: NCT06268535. Among 36,580,288 database reports, 42,828 CTRCD cases associated with at least one anticancer drug were identified with death reported in 20.6% of cases (8,833 CTRCD cases). Primary analysis revealed 25 anticancer drugs significantly associated with CTRCD reporting, with trastuzumab, doxorubicin, and bortezomib exhibiting the strongest associations. CTRCD reporting was associated with kinase inhibitors, including BCR-ABL inhibitors, ibrutinib and osimertinib. New signals were identified for trabectedin, clofarabine, fludarabine, entrectinib, gemtuzumab ozogamicin, and anagrelide. In contrast, immune checkpoint inhibitors and most anti-vascular endothelial growth factor therapies showed no association with CTRCD.
This disproportionality study identified 25 anticancer drugs significantly associated with CTRCD reporting, including new signals. It highlights discrepancies compared to drugs recommended for cardiac dysfunction evaluation in the 2022 ESC Guidelines. This underscores the importance of including CTRCD as a safety endpoint in cancer studies.
Accepted manuscripts
