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Original Investigation
October 2016

Trastuzumab-Related Cardiotoxic Effects in Taiwanese Women: A Nationwide Cohort Study

Author Affiliations
  • 1Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
  • 2Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
  • 3Health Outcome Research Center, National Cheng Kung University, Tainan, Taiwan
JAMA Oncol. 2016;2(10):1317-1325. doi:10.1001/jamaoncol.2016.1269
Key Points

Question  What is the incidence and risk of heart failure (HF) and/or cardiomyopathy (CM) among Asian trastuzumab users with breast cancer?

Findings  In this nationwide cohort study of Taiwanese women with incident breast cancer the crude incidence of HF and/or CM was significantly higher in trastuzumab users compared with nonusers.

Meaning  The findings provide critical trastuzumab cardiac safety information for Asian patients with breast cancer.

Abstract

Importance  Trastuzumab is an essential medicine per the World Health Organization Model List, but its cardiac safety information in Asian women is limited.

Objective  To estimate the rate and the risk of heart failure (HF) and/or cardiomyopathy (CM) in Asian women undergoing trastuzumab treatment.

Design  This cohort study used the Taiwanese National Health Insurance Research Database (NHIRD), a nationwide claim database covering more than 99% of the entire Taiwanese population, to identify 23 006 women with incident breast cancer (BC) who received chemotherapy from 2006 to 2009. We grouped women per their initial treatment regimens and found 1066 new trastuzumab users. We matched trastuzumab users with nonusers by year of BC diagnosis and propensity score (PS) with the caliper widths at 0.25 standard deviation of PS (up to 4 nonusers per trastuzumab user). The study lasted from January 2006 to December 2013 with a median follow-up of 5.29 years and a landmark design to avoid immortal time bias.

Exposure  Trastuzumab.

Main Outcomes and Measures  To estimate HF and/or CM rates and time to HF and/or CM, we employed a cause-specific hazard model. Trastuzumab exposure was a time-dependent variable, while cumulative courses of chemotherapy agents with known cardiotoxic effects (including anthracyclines, taxanes, and cyclophosphamide) were defined as time-dependent covariates in the analysis model. We also performed 6 sensitivity analyses.

Results  In this cohort of 23 006 women (mean age, 50.99 years), the crude incidence of HF and/or CM was 4.03% in trastuzumab users and 2.88% in nonusers. The median time to HF and/or CM was 456 days in trastuzumab users and 966 days in nonusers. The 1-year cumulative hazard ratio was 1.86 (95% CI, 1.08-3.19). The sensitivity analyses yielded similar results.

Conclusions and Relevance  Compared with the published results, the trastuzumab-related HF and/or CM rate was 5-fold lower in Taiwanese women with breast cancer. Nonetheless, our cohort had a similar trastuzumab-related HF and/or CM risk. Our study provides critical cardiac safety information of trastuzumab for Asian women with BC under current treatment guidelines and label information.

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