Trastuzumab versus lapatinib: the cardiac side of the story
Hamdy Azim1, Hatem A Azim, Bernard Escudier
1Department of Clinical Oncology, Cairo University Hospital, Cairo, Egypt.
Abstract:
HER2 gene plays a pivotal role in the pathogenesis of 20% of breast cancer patients. At the same time, it is one of the main cardiac survival pathways when subjected to bio-mechanical stress including exposure to anthracyclines. With the emergence of the anti-HER2 targeting agents, concerns raised regarding the potential cardiac toxicities of these drugs. In the early clinical trials with trastuzumab, it was evident that it has a significant cardiac toxicity. The incidence of symptomatic heart failure ranged from 4% to 7% with trastuzumab alone, and 27% when administered concurrently with doxorubicin. On the other hand, available data suggest that lapatinib is much less cardiotoxic. The incidence of symptomatic heart failure has been constantly reported to be less than 0.5%. In this review, we discuss the possible theories behind the differences in the cardiac profile of both agents. We emphasize on the role of cardiac bioenergetics and the effects of trastuzumab and lapatinib on ATP production through the different effects they exert on the cardiac mitochondria.
Insights
Trastuzumab and lapatinib target HER2 in breast cancer but have different cardiac safety profiles. This review explores their effects on cardiac mitochondria and ATP production, explaining lapatinib
Area of Science:
- Oncology
- Cardiology
- Pharmacology
Background:
- HER2 gene is crucial in 20% of breast cancers and cardiac survival pathways.
- Anti-HER2 agents raise concerns about potential cardiac toxicities.
- Trastuzumab shows significant cardiac toxicity, while lapatinib appears less cardiotoxic.
Purpose of the Study:
- To explore theories behind the differing cardiac profiles of trastuzumab and lapatinib.
- To emphasize the role of cardiac bioenergetics in drug-induced cardiotoxicity.
- To investigate the effects of these agents on ATP production in cardiac mitochondria.
Main Methods:
- Review of existing clinical trial data on trastuzumab and lapatinib cardiotoxicity.
- Discussion of proposed mechanisms of cardiac toxicity.
- Focus on the impact on cardiac mitochondrial function and energy production.
Main Results:
- Trastuzumab is associated with symptomatic heart failure in 4-7% of patients (up to 27% with doxorubicin).
- Lapatinib demonstrates significantly lower cardiotoxicity, with <0.5% incidence of symptomatic heart failure.
- Differences in cardiac profiles may relate to distinct effects on cardiac mitochondria and ATP production.
Conclusions:
- Trastuzumab and lapatinib exhibit distinct cardiac safety profiles.
- Cardiac bioenergetics and mitochondrial effects are key factors in understanding these differences.
- Further research into these mechanisms can guide safer anti-HER2 therapy selection.
