TY - JOUR
T1 - Cardiac toxicity of ErbB2-targeted therapies
T2 - What do we know?
AU - Perez, Edith A.
N1 - Funding Information:
This article includes discussion of investigational and/or unlabeled uses of drugs, including the use of trastuzumab plus lapatinib with chemotherapy, lapatinib alone, or trastuzumab plus docetaxel and carboplatin for the adjuvant treatment of breast cancer; lapatinib plus trastuzumab for metastatic breast cancer; and lapatinib alone for breast cancer or other solid tumors. Dr Perez has received research support from Genentech BioOncology, GlaxoSmithKline, Bristol-Myers Squibb, sanofi-aventis, Pfizer, and Novartis Oncology.
PY - 2008/3
Y1 - 2008/3
N2 - The potential for cardiac toxicity in association with targeted biologic agents was first observed with trastuzumab, a monoclonal antibody that targets the ErbB2/HER2 receptor. In the pivotal trial of trastuzumab in ErbB2-positive metastatic cancer, an increased incidence of serious cardiac events was observed, particularly when trastuzumab was administered in combination with anthracyclines. The ErbB2 receptor is expressed on cardiomyocytes, in addition to tumor tissue, where it exerts a protective effect on cardiac function; thus, interference with ErbB2-signaling may block this protective effect. However, in contrast to anthracycline-induced cardiac toxicity, trastuzumab-related cardiac dysfunction does not appear to increase with cumulative dose or to be associated with ultrastructural changes in the myocardium and is generally reversible. When used in adjuvant regimens for the treatment of ErbB2-positive early-stage breast cancer, trastuzumab has been shown to significantly improve disease-free and overall survival. The incidence of class III/IV congestive heart failure (CHF) ranged from 0.4%-3.8% in the major adjuvant trastuzumab trials. More recently, small-molecule tyrosine kinase inhibitors such as lapatinib have been investigated for the treatment of ErbB2-positive metastatic breast cancer. In a comprehensive analysis of cardiac safety data from all lapatinib trials completed to date, which included 3558 healthy volunteers and patients with a variety of solid cancers on 43 trials, the overall incidence of left ventricular ejection fraction declines was 1.6%, with 0.2% of patients experiencing symptomatic CHF. Risk factors that might predict for cardiac dysfunction with ErbB2-targeted therapy are actively under investigation and will aid in the identification of at-risk populations and in the development of strategies for risk minimization in the future. It is important to note that, while careful cardiac monitoring is required for all patients receiving ErbB2-targeted therapy in any disease setting, the overall impact of these agents on the outcomes of patients with ErbB2-positive breast cancer has been dramatic and positive.
AB - The potential for cardiac toxicity in association with targeted biologic agents was first observed with trastuzumab, a monoclonal antibody that targets the ErbB2/HER2 receptor. In the pivotal trial of trastuzumab in ErbB2-positive metastatic cancer, an increased incidence of serious cardiac events was observed, particularly when trastuzumab was administered in combination with anthracyclines. The ErbB2 receptor is expressed on cardiomyocytes, in addition to tumor tissue, where it exerts a protective effect on cardiac function; thus, interference with ErbB2-signaling may block this protective effect. However, in contrast to anthracycline-induced cardiac toxicity, trastuzumab-related cardiac dysfunction does not appear to increase with cumulative dose or to be associated with ultrastructural changes in the myocardium and is generally reversible. When used in adjuvant regimens for the treatment of ErbB2-positive early-stage breast cancer, trastuzumab has been shown to significantly improve disease-free and overall survival. The incidence of class III/IV congestive heart failure (CHF) ranged from 0.4%-3.8% in the major adjuvant trastuzumab trials. More recently, small-molecule tyrosine kinase inhibitors such as lapatinib have been investigated for the treatment of ErbB2-positive metastatic breast cancer. In a comprehensive analysis of cardiac safety data from all lapatinib trials completed to date, which included 3558 healthy volunteers and patients with a variety of solid cancers on 43 trials, the overall incidence of left ventricular ejection fraction declines was 1.6%, with 0.2% of patients experiencing symptomatic CHF. Risk factors that might predict for cardiac dysfunction with ErbB2-targeted therapy are actively under investigation and will aid in the identification of at-risk populations and in the development of strategies for risk minimization in the future. It is important to note that, while careful cardiac monitoring is required for all patients receiving ErbB2-targeted therapy in any disease setting, the overall impact of these agents on the outcomes of patients with ErbB2-positive breast cancer has been dramatic and positive.
KW - Brain natriuretic peptide
KW - Lapatinib
KW - Trastuzumab
KW - Troponin I
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UR - http://www.scopus.com/inward/citedby.url?scp=42449155137&partnerID=8YFLogxK
U2 - 10.3816/CBC.2008.s.007
DO - 10.3816/CBC.2008.s.007
M3 - Article
C2 - 18777950
AN - SCOPUS:42449155137
SN - 1526-8209
VL - 8
SP - S114-S120
JO - Clinical breast cancer
JF - Clinical breast cancer
IS - SUPPL. 3
ER -