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Cardiac dysfunction in the trastuzumab clinical trials experience
Andrew Seidman1, Clifford Hudis, Mary Kathryn Pierri
1Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. seidmana@mskcc.org
Summary
Trastuzumab increases cardiac dysfunction (CD) risk, especially with concurrent anthracyclines. However, the survival benefits for metastatic breast cancer often outweigh this risk.
Area of Science:
- Cardiology
- Oncology
- Pharmacology
Background:
- Trastuzumab is a targeted therapy for HER2-positive cancers.
- Cardiac dysfunction (CD) is a known potential side effect of cancer therapies.
- Understanding CD risk factors is crucial for patient management.
Purpose of the Study:
- To estimate cardiac dysfunction risk in patients receiving trastuzumab.
- To characterize CD severity, treatment, and outcomes.
- To assess the impact of baseline factors and cumulative drug doses on CD.
Main Methods:
- Retrospective review of patients from seven phase II and III trastuzumab trials.
- Diagnosis of CD based on predefined criteria.
- Severity documented using the New York Heart Association classification system.
- Cumulative drug doses analyzed using product-limit estimates.
Main Results:
- Trastuzumab use is associated with increased CD risk.
- Highest incidence (27%) observed with concurrent trastuzumab and anthracycline plus cyclophosphamide.
- Lower incidence with paclitaxel and trastuzumab (13%) or trastuzumab alone (3-7%).
- Most symptomatic CD patients (75%) improved with standard heart failure treatment (79%).
Conclusions:
- Trastuzumab elevates cardiac dysfunction risk, particularly when combined with anthracyclines.
- For metastatic breast cancer, trastuzumab's survival benefits often justify the cardiac risk.
- Risk-benefit assessment is essential for personalized patient care.