Detection and evaluation of post-marketing cardiovascular toxicity signals associated with antibody-drug conjugates based on disproportionality analysis
YIN Yue-song
JIN Hui-xin
GUO Shao-wei
XU Xiao-fei
WU Yu-pei
ZHANG Li-na
QIU Zhi-hong
LI Qing-xia
Abstract：Objective:To conduct data mining on the adverse events associated with antibody-drug conjugate(ADC)based upon the US FDA adverse event reporting system(FAERS)to provide references for the safety assessment of ADC.Methods:Based on the FAERS database,cardiovascular adverse events(AEs)reports related to ADC were collected from the third quarter of 2011(Q3)to the third quarter of 2024(Q3).Cardiovascular AEs were grouped into nine narrow categories using the standardized Medical Dictionary for Regulatory Activities(MedDRA)Queries(SMQ).The AEs signals were detected and evaluated with reporting odds ratio(ROR)and information component(IC).Results:A total of 2 442 reports of cardiovascular AEs were extracted with eight ADC drugs as the primary suspected drugs.Based on the SMQ,positive signals were detected for trastuzumab deruxtecan,trastuzumab emtansine,brentuximab vedotin,inotuzumab ozogamicin,and polatuzumab vedotin.At the preferred terms level,seven ADC drugs except mirvetuximab soravtansine showed positive signals for cardiovascular AEs,involving a total of 32 PT.The median time to onset of cardiovascular AEs for the eight ADC,from the shortest to the longest,was as follows:polatuzumab vedotin(17 days),enfortumab vedotin(17 days),sacituzumab govitecan(22.5 days),brentuximab vedotin(27.5 days),trastuzumab deruxtecan(47 days),inotuzumab ozogamicin(60.5 days),mirvetuximab soravtansine(61 days),and trastuzumab emtansine(70.5 days).Conclusion:The risk of cardiovascular AEs varies among different ADC,often occurring in the early stage of treatment.So the clinical use of ADC requires close monitoring and assessment of cardiovascular AEs according to drug efficacy,risk,and patient-specific conditions.
Keywords：antibody-drug conjugatecardiovascular adverse eventsUS FDA adverse event reporting systemsignal mining
Publication Date：2025-10-30
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：9( 2224-2232 )