Adverse cardiac events associated with antibody-drug conjugates in cancer patients: retrospective analysis of FAERS database and RCTs

Abstract Antibody-drug conjugates (ADCs) are approved for use in cancers. Cardiovascular adverse reaction is a fatal adverse reaction associated with ADCs. The incidence of adverse cardiac events about ADCs has not been fully studied. We aimed to assess differences in cardiotoxicity among cancer patients treated with different ADCs. An observational retrospective pharmacovigilance study of ADC-related adverse cardiac events was conducted based on the FDA Adverse Event Reporting System (FAERS) and Open tools for data mining and analysis of pharmacoVigilance data (OpenVigil 2.1) website. We conducted a comprehensive search of articles published before 24 January 2024, using PubMed, Web of Science, Cochrane Library, Scopus, CINAHL, Embase databases, and the Clinical Trials website (https://clinicaltrials.gov). Primary outcomes include any cardiotoxicity. Secondary outcomes focused on heart failure. Network meta-analysis and subgroup analyses were conducted to synthesize results based on relative risk (RR) values. Surface under the cumulative ranking curve (SUCRA) values were calculated for risk ranking among ADCs according to the types and target of ADCs. A total of 1522 cases of cardiac adverse events from FAERS associated with ADC treatments. All ADCs showed disproportionate association in cardiac adverse events. Gender and age factors are considered to have an influential role in the cardiotoxicity induced by ADCs. The network meta-analysis showed that the overall incidence rate was 17.12% [95% confidence interval (CI): 13.36%, 20.88%]. Brentuximab vedotin has the RR value of 1.78 (95% CI: 1.13, 2.82). HER-2-targeted ADCs have the RR value of 0.61 (95% CI: 0.42, 0.89). Polatuzumab vedotin and enfortumab vedotin have SUCRA values of 82.6 and 22.0, respectively. The SUCRA values of ADC targeting FRα and TROP-2 were 75.6 and 18.8, respectively. Cardiac adverse events are associated with ADCs. ADCs targeting HER-2 show lower cardiac toxicity. Brentuximab vedotin is associated with higher cardiac toxicity. Polatuzumab vedotin has the highest risk for cardiac toxicity, and enfortumab vedotin has the lowest risk. ADC targeting FRα has the highest risk of cardiotoxicity, and ADC targeting TROP-2 has the lowest risk.