title: Cardiotoxicity in targeted therapy for breast cancer: A study of the FDA adverse event reporting system (FAERS).
abstract: Purpose Cancer chemotherapy-induced cardiotoxicity is concerning. Certain anthracyclines and targeted therapies are known to have potential for cardiotoxicity, but existing trial evidence is inadequate to understand real-world patterns of cardiotoxicity with newer targeted therapies and their common combinations with older agents. This study evaluated chemotherapy-related cardiotoxicity reports for targeted therapies and their combinations in breast cancer patients. Methods The US Food and Drug Administration Adverse Event Reporting System (FAERS) database from January 2004 through September 2012 was used to summarize characteristics of reported cardiotoxicity events and their health outcomes. Disproportionality analyses with reporting odds ratios (ROR) and 95% confidence intervals (95% CI) were conducted to detect event signals using a case/non-case method for each targeted therapy and combination. Results A total of 59,739 cases of cardiotoxicity reports were identified; 937 cases identified targeted therapy as the suspect drug. Trastuzumab had the highest number of reports followed by bevacizumab and lapatinib. Proportions of reports of death and disability outcomes for each targeted therapy were approximately 20-25% of the total reports of serious events. Trastuzumab had the highest ROR as a single agent (ROR = 5.74; 95% CI = 5.29-6.23) or combination use of cyclophosphamide (ROR = 16.83; 95% CI = 13.32-21.26) or doxorubicin (ROR = 17.84; 95% CI = 13.77-23.11). Relatively low cardiotoxicity reporting rates were found with lapatinib, regardless of use with combination therapy. Conclusions Analysis of FAERS data identified signals for adverse cardiotoxicity events with targeted therapies and their combinations. Practitioners should consider factors that may increase the likelihood of cardiotoxicity when assessing treatment. Findings support continued surveillance, risk factor identification, and comparative studies.
authors.affiliation: 1 Harrison School of Pharmacy, Auburn University, Auburn, AL, USA.
authors.forename: Saranrat
authors.initials: S
authors.lastname: Wittayanukorn
authors.affiliation: 1 Harrison School of Pharmacy, Auburn University, Auburn, AL, USA.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Qian
authors.affiliation: 2 Department of Internal Medicine, East Alabama Medical Center, AL, USA.|3 Edward via College of Osteopathic Medicine, AL, USA.
authors.forename: Brandon S
authors.initials: BS
authors.lastname: Johnson
authors.affiliation: 1 Harrison School of Pharmacy, Auburn University, Auburn, AL, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hansen
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D066126:Cardiotoxicity / Q000209:etiology*; D002986:Clinical Trials as Topic; D016208:Databases, Factual / Q000706:statistics & numerical data; D004359:Drug Therapy, Combination / Q000009:adverse effects*; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D016017:Odds Ratio; D011358:Product Surveillance, Postmarketing; D012307:Risk Factors; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents
keywords: Cardiotoxicity; adverse drug reaction reporting system; adverse events; breast cancer; targeted therapy