Related Experiment Video
Updated: Sep 13, 2025
Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery
Published on: April 26, 2024
Toxicity Profiles of Antibody-Drug Conjugates: Synthesis and Graphical Insights to Optimize Patient-Centered
Bérénice Collineau1, Anthony Gonçalves1,2,3, Marie Domon4
1Institut Paoli-Calmettes, Department of Medical Oncology, 13009 Marseille, France.
Background:
The treatment options for HER2-negative metastatic breast cancer include targeted therapies, cytotoxic chemotherapies, and immunotherapy. However, limited specificity and inevitable resistance highlight the need for novel agents. Antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), represent a breakthrough by selectively delivering cytotoxic agents to tumor cells, potentially improving the therapeutic index. Despite demonstrated efficacy, ADCs present toxicity profiles similar to conventional chemotherapy, alongside unique adverse events. In clinical practice, oncologists may face scenarios where both T-DXd and SG are treatment options in HER2-negative mBC. To enable shared decision-making, it is crucial to present a comprehensive overview that includes both efficacy data and detailed toxicity profiles. Our objective was to provide a pooled and informative synthesis of toxicities from pivotal studies, including graphical representations, to support informed, patient-centered medical decisions.
Methods:
We reviewed safety data from phase 3 clinical trials in HER2-negative mBC: DESTINY-Breast04/DESTINY-Breast06 for T-DXd and ASCENT/TROPICS-02 for SG. Adverse event (AE) profiles, including frequency and severity, were extracted, and weighted means were calculated. Emerging ADCs such as datopotamab deruxtecan and patritumab deruxtecan were considered to contextualize future therapeutic decisions.
Results:
Tables, bar plots and radar plots were generated. T-DXd demonstrated high rates of nausea (69.2%), fatigue (47.2%), and neutropenia (35.6%), with 52.7% experiencing grade ≥ 3 AEs. Notably, pneumonitis occurred in 10.7%, with grade ≥ 3 in 2.6%. SG showed a distinct AE profile, with higher incidences of neutropenia (67.1%), with grade ≥ 3 in 51.3%, and diarrhea (60.8%).
Conclusions:
The choice between ADCs in HER2-negative metastatic BC when both T-DXd and SG are treatment options should consider toxicity profiles to optimize patient-centered treatment strategies. Tailoring ADC selection based on individual tolerance and preferences is critical for shared decision-making, and future research should focus on assessing the utility and acceptability of such clinical tools to guide treatment selection.
Insights
Choosing between antibody-drug conjugates (ADCs) like trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) for HER2-negative metastatic breast cancer requires careful consideration of their distinct toxicity profiles to guide patient-centered treatment decisions.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- HER2-negative metastatic breast cancer (mBC) treatment relies on therapies with limited specificity and potential resistance.
- Antibody-drug conjugates (ADCs) offer targeted delivery of cytotoxic agents, improving the therapeutic index.
- Despite efficacy, ADCs share chemotherapy-like toxicities and unique adverse events, necessitating comparative safety data.
Purpose of the Study:
- To provide a pooled synthesis of toxicity data from pivotal trials of T-DXd and SG in HER2-negative mBC.
- To facilitate shared decision-making by presenting comprehensive efficacy and toxicity profiles.
- To support informed, patient-centered medical decisions regarding ADC selection.
Main Methods:
- Safety data from Phase 3 trials (DESTINY-Breast04/06 for T-DXd, ASCENT/TROPICS-02 for SG) were reviewed.
- Adverse event (AE) profiles, including frequency and severity, were extracted and analyzed.
- Emerging ADCs were considered for future therapeutic context.
Main Results:
- T-DXd showed high rates of nausea (69.2%), fatigue (47.2%), and neutropenia (35.6%), with 52.7% experiencing grade ≥ 3 AEs. Pneumonitis occurred in 10.7% (grade ≥ 3 in 2.6%).
- SG presented a distinct profile with higher incidences of neutropenia (67.1%, grade ≥ 3 in 51.3%) and diarrhea (60.8%).
- Graphical representations (tables, bar plots, radar plots) were generated to visualize AE data.
Conclusions:
- ADC selection in HER2-negative mBC should prioritize toxicity profiles for optimized patient-centered strategies.
- Tailoring ADC choice to individual patient tolerance and preferences is crucial for shared decision-making.
- Future research should evaluate clinical tools that guide ADC treatment selection based on patient-specific factors.
More Related Videos
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
11:58Initial Evaluation of Antibody-conjugates Modified with Viral-derived Peptides for Increasing Cellular Accumulation and Improving Tumor Targeting
Published on: March 8, 2018
