Abstract 107: Cardiovascular Events, Early Discontinuation of Trastuzumab, and Their Impact on Survival

Abstract

Background: Trastuzumab increases risk of cardiovascular (CV) events such as heart failure (HF) in clinical trials. However, it is unknown how often trastuzumab therapy is ended early (i.e. early discontinuation), which CV events are associated with early discontinuation, and how CV events and early discontinuation affect overall survival among older women with breast cancer. Methods: Using the Surveillance, Epidemiology, and End Results-Medicare dataset, we identified women age 67-94 with stage I-III breast cancer diagnosed 2005-2009 who received trastuzumab adjuvant chemotherapy and followed them through 2011. Completed trastuzumab treatment was defined as ≥11 months of continuous trastuzumab treatments with no delay between trastuzumab treatments >45 days. We identified therapy-associated CV events as those occurring within 45 days before or after the last trastuzumab treatment. We compared CV events between the completed and early discontinuation groups using chi-squared statistics. We used Cox proportional hazard models to examine the association of overall survival with early discontinuation of trastuzumab treatment and CV events. Results: Our cohort consisted of 585 women (mean age: 71.6 years), with a median follow-up of 4.2 years. Approximately 41% (239) of women did not complete trastuzumab therapy. Patients with early discontinuation of trastuzumab treatment were more likely to have HF/cardiomyopathy (18.8% vs. 4.0%; p<.001), atrial fibrillation (5.4% vs. <3.2%, p=.006), and other cardiovascular events (7.9% vs. 3.5%; p=.017) within 45 days before or after the last trastuzumab treatment. These cardiovascular events were strongly associated with worse survival (adjusted hazard ratio [AHR] 3.54; 95% CI 1.87 to 6.68). Women with early discontinuation of trastuzumab treatment were also more likely to have worse overall survival, but the results were not statistically significant (AHR: 1.74; 95% CI 0.94 to 3.23). Conclusion: Early discontinuation of trastuzumab treatment is common among older women with breast cancer, and associated with higher rates of CV events. Reducing CV complications from trastuzumab therapy will likely improve overall survival in patients with breast cancer