# Identification of anticancer drugs associated to cancer therapy-related cardiac dysfunction: a VigiBase® disproportionality analysis

## TL;DR

This study identifies 25 anticancer drugs linked to heart-related side effects using global safety reports, highlighting new risks and discrepancies with current guidelines.

## Contribution

The study identifies new anticancer drugs associated with cancer therapy-related cardiac dysfunction using disproportionality analysis in a global adverse event database.

## Key findings

- 25 anticancer drugs were significantly associated with cancer therapy-related cardiac dysfunction (CTRCD) reporting.
- Trastuzumab, doxorubicin, and bortezomib showed the strongest associations with CTRCD.
- New signals for CTRCD were identified for drugs like trabectedin, clofarabine, and entrectinib.

## 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 29 February 2024. Reporting odds ratios for CTRCD were evaluated using a stepwise selection procedure and multivariable-adjusted analyses. Subsequently, secondary analyses consisted of the description 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 (8833 CTRCD cases). Primary analysis revealed 25 anticancer drugs significantly associated with CTRCD reporting, with trastuzumab, doxorubicin, and bortezomib exhibiting the strongest associations. Cancer therapy-related cardiac dysfunction 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 with 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.

Graphical AbstractSignificant associations between cancer therapy-related cardiac dysfunction cases and anticancer drugs in VigiBase® in the primary analysis population, using the primary analysis (stepwise selection procedure). Only the 25 anticancer drugs significantly associated with CTRCD are displayed among the 280 anticancer drugs. Drugs in grey areas represent new signals. CTRCD, cancer therapy-related cardiac dysfunction and ROR, reporting odd-ratio.

Significant associations between cancer therapy-related cardiac dysfunction cases and anticancer drugs in VigiBase® in the primary analysis population, using the primary analysis (stepwise selection procedure). Only the 25 anticancer drugs significantly associated with CTRCD are displayed among the 280 anticancer drugs. Drugs in grey areas represent new signals. CTRCD, cancer therapy-related cardiac dysfunction and ROR, reporting odd-ratio.