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.

Trastuzumab cardiotoxicity in HER2-positive breast cancer patients in tertiary health care center, sultanate of Oman

“…In fact, this observation was associated with Trastuzumab. (44) Hypertension, the most extensively studied comorbidity in this patients' population, is a generally accepted risk factor and its importance was confirmed in several studies. (31) Nevertheless, the results are not uniform and there are studies that, like this study, could not demonstrate its predictive role.…”

The Current Landscape of Clinical Studies Focusing on Thyroid Cancer: A Comprehensive Analysis of Study Characteristics and Their Publication Status

“…Nonetheless, none of the targeted drugs have shown significant benefit in OS, except for a subgroup of patients receiving lenvatinib or cabozantinib (17,18). Regardless of the limited treatment effect, a high rate of adverse events was observed in patients who received targeted therapy (19,20). Immunotherapy, including immune cells and checkpoint inhibitors, may provide a new alternative option for TC with poor prognosis, as it has shown survival benefit in other oncology studies (21,22).…”

Validating the pharmacogenomics of chemotherapy-induced cardiotoxicity: What is missing?

“…These directed anticancer agents are currently widely used and constitute three of the leading chemotherapy revenues in the USA, in that bevacizumab, and trastuzumab revenues in 2014/2015 in the USA alone were $3 billion, and $2.4 billion, respectively (statista.com). Despite their broad utilization in cancer treatment, FAERS database reported that between 2004 and 2010, trastuzumab had highest number of cardiotoxicity reports followed by bevacizumab (Wittayanukorn et al, 2015). …”