Related Experiment Video
Updated: Jan 9, 2026
Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery
Published on: April 26, 2024
HER2-Targeted Antibody-Drug Conjugate Toxicities in Breast Cancer
Seohyuk Lee1,2, Adriana M Kahn1, Mariya Rozenblit1
1Department of Internal Medicine, Section of Medical Oncology, Yale University, New Haven, Connecticut, USA.
Background:
HER2-targeted antibody-drug conjugates (ADCs) have dramatically advanced breast cancer outcomes. Two HER2-targeted ADCs, trastuzumab deruxtecan and trastuzumab emtansine, are currently approved for use in breast cancer, with > 60 other candidates under ongoing investigation.
Methods:
In this report, we provide a narrative review of existing data underlying the current understanding of HER2-targeted ADC toxicities in breast cancer, highlighting both common and serious adverse events.
Results:
When used as an adjuvant or neoadjuvant, first- or second-line agent, alone or in combination with another agent, trastuzumab emtansine has been commonly associated with epistaxis, fatigue, headache, nausea, and pyrexia across several clinical trials. Comparatively, trastuzumab deruxtecan has been commonly associated with alopecia, cytopenias, decreased appetite, fatigue, and gastrointestinal adverse effects.
Conclusion:
Despite the demonstrated clinical benefits in breast cancer, diverse systemic and organ-specific adverse events, including dose-limiting toxicities, have been reported even at suboptimal therapeutic doses and pose significant barriers to pursuing dose escalations for maximizing therapeutic efficacy.
Insights
HER2-targeted antibody-drug conjugates (ADCs) improve breast cancer outcomes but cause toxicities. Understanding these adverse events is crucial for optimizing treatment efficacy and patient safety.
Area of Science:
- Oncology
- Pharmacology
Background:
- HER2-targeted antibody-drug conjugates (ADCs) represent a significant advancement in breast cancer treatment.
- Two approved ADCs, trastuzumab deruxtecan and trastuzumab emtansine, are widely used, with over 60 additional candidates in development.
Purpose of the Study:
- To review current data on the toxicities associated with HER2-targeted ADCs in breast cancer.
- To highlight common and serious adverse events, as well as dose-limiting toxicities.
Main Methods:
- A narrative review of existing clinical trial data.
- Focus on adverse events reported for trastuzumab emtansine and trastuzumab deruxtecan.
Main Results:
- Trastuzumab emtansine is associated with epistaxis, fatigue, headache, nausea, and pyrexia.
- Trastuzumab deruxtecan commonly causes alopecia, cytopenias, decreased appetite, fatigue, and gastrointestinal issues.
- Adverse events occur even at suboptimal doses, limiting dose escalation for maximal efficacy.
Conclusions:
- Despite clinical benefits, HER2-targeted ADCs cause diverse systemic and organ-specific toxicities.
- These adverse events, including dose-limiting toxicities, pose barriers to maximizing therapeutic efficacy.
- Further research is needed to mitigate ADC-related toxicities in breast cancer patients.
More Related Videos
13:59High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds
Published on: August 18, 2023
14:20Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:28Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...