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


METHODS
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.


METHODS
Trastuzumab.


METHODS
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
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.
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland2Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan3Health Outcome Research Center, National Cheng Kung University, Tainan, Taiwan.
Hsu-Chih
HC
Chien
Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan3Health Outcome Research Center, National Cheng Kung University, Tainan, Taiwan.
Yea-Huei
YH
Kao Yang
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
Jane P F
JP
Bai
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000453:epidemiology; D005260:Female; D006333:Heart Failure / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D016016:Proportional Hazards Models; D013624:Taiwan / Q000453:epidemiology; D000068878:Trastuzumab / Q000009:adverse effects* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D000068878:Trastuzumab