Related Experiment Video
Updated: Sep 9, 2025
Measurement of Antibody Effects on Cellular Function of Isolated Cardiomyocytes
Published on: March 8, 2013
Systematic analysis and mechanistic investigation of cardiac adverse events associated with antibody-drug conjugates
Xiaohan Zheng1, Yongzhen Song1, Yong Cao1
1Department of Biostatistics, School of Public Health, Harbin Medical University, Harbin, China.
Background:
Antibody-drug conjugate (ADC), combining monoclonal antibodies with cytotoxic payloads through covalent linkers, is leading a new era of targeted cancer therapy. Despite its therapeutic success, cardiotoxicity has been a recognized concern in early approved ADCs such as trastuzumab, yet the cardiac safety profiles and mechanisms of recently approved ADCs remain poorly characterized. Assessing the nature of their cardiac events using the FDA Adverse Event Reporting System (FAERS) database is vital for risk assessment in surgical oncology. This study aimed to analyze cardiac adverse events (cAEs) related to ADCs in the FAERS database to detect cardiac risk signals, characterize clinical patterns, and investigate mechanistic pathways, ultimately informing risk mitigation strategies in clinical practice.
Materials And Methods:
This systematic study analyzed FAERS data (Jan 2019-Sep 2023) for ADC-related adverse events (AEs). AEs were standardized using MedDRA terminology. Disproportionality analysis using the reporting odds ratio (ROR) method was performed to identify ADC-related cAEs. Potential risk factors were evaluated through logistic regression analyses. To understand the molecular basis, TCGA transcriptome data were analyzed to explore mechanisms of ADC-related cAEs.
Results:
cAEs comprised 11.77% (range: 8.63-23.50%) of all ADC-related reports from 2019 to 2023. A total of 49 cAE categories were identified. The mean age of reports with ADC-related cAEs was 60 (±13) years with 8.67% of reports having a fatal outcome. Breast cancer indications dominated. Combining ADCs with dexamethasone significantly reduced the risk of cardiac failure (ROR decreased from 3.18 to 0.85). ADC-related cAEs correlated with dysregulated HSP70 binding ( R = 0.82, P = 4.66e-4) and heat shock protein pathways.
Conclusions:
This study underscores the importance of recognizing and managing the cAEs associated with ADC therapy. Our findings provide a nuanced understanding of the burden, risk factors, and potential biological mechanisms of ADC-related cAEs, which can inform clinical decision-making and guide the development of safer and more effective ADC therapies.
Insights
Antibody-drug conjugates (ADCs) can cause cardiac adverse events, with recent ADCs showing poorly characterized safety profiles. This study analyzed FAERS data, revealing cardiac risks and potential mechanisms involving heat shock proteins, informing safer ADC development.
Area of Science:
- Oncology
- Pharmacology
- Cardiology
Background:
- Antibody-drug conjugates (ADCs) represent a significant advancement in targeted cancer therapy.
- While effective, ADCs carry a risk of cardiotoxicity, a concern noted in earlier agents.
- The cardiac safety and mechanisms of recently approved ADCs require thorough investigation for surgical oncology risk assessment.
Purpose of the Study:
- To analyze cardiac adverse events (cAEs) associated with ADCs using the FDA Adverse Event Reporting System (FAERS) database.
- To identify cardiac risk signals, characterize clinical patterns, and investigate potential mechanistic pathways of ADC-related cAEs.
- To inform risk mitigation strategies for ADC therapy in clinical practice.
Main Methods:
- Systematic analysis of FAERS data from January 2019 to September 2023 for ADC-related adverse events.
- Standardization of adverse events using MedDRA terminology and disproportionality analysis (Reporting Odds Ratio) to detect cAEs.
- Logistic regression for risk factor evaluation and TCGA transcriptome data analysis to explore molecular mechanisms.
Main Results:
- Cardiac adverse events constituted 11.77% of all ADC-related reports between 2019-2023, with 49 identified cAE categories.
- The mean age of patients with ADC-related cAEs was 60, with 8.67% resulting in fatal outcomes; breast cancer was the predominant indication.
- Concomitant use of dexamethasone with ADCs reduced the risk of cardiac failure (ROR from 3.18 to 0.85), and cAEs correlated with dysregulated HSP70 binding and heat shock protein pathways.
Conclusions:
- Recognizing and managing ADC-related cardiac adverse events is crucial for patient safety.
- The study provides insights into the burden, risk factors, and biological mechanisms of ADC-related cAEs.
- Findings can guide clinical decision-making and the development of safer, more effective ADC therapies.
More Related Videos
10:39Automated Contraction Analysis of Human Engineered Heart Tissue for Cardiac Drug Safety Screening
Published on: April 15, 2017
11:02Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction
Published on: September 14, 2018
Related Concept Videos
01:19Pharmacovigilance
This process, termed pharmacovigilance, aims to detect, evaluate, and minimize harmful effects related to medication use. The data collection for pharmacovigilance depends on spontaneous reporting systems, where healthcare professionals or patients voluntarily report suspected ADRs.
In some cases, there...
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:28Structure-Activity Relationships and Drug Design
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
01:30Acute Coronary Syndrome III: Diagnostic Studies
01:29Heart Failure II: Pathophysiology