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Erschienen in:
01.06.2016 | Clinical Trial
Long-term cardiovascular outcomes and overall survival of early-stage breast cancer patients with early discontinuation of trastuzumab: a population-based study
Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2016
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We critically examined long-term cardiovascular (CV) outcomes and overall survival (OS) of breast cancer (BC) patients who had cardiotoxicity during adjuvant trastuzumab treatment requiring discontinuation in a population-based sample. This was a retrospective cohort of early-stage BC patients diagnosed before 2010 and treated with trastuzumab in Ontario. Patients were stratified based on trastuzumab doses received: 1–8, 9–15, ≥16 (therapy completion). Time-dependent multivariable Cox models were used to analyze primary endpoint OS, and the following composite endpoints: hospitalization/emergency room visit for heart failure (HF) or death; non-HF CV (myocardial infarction, stroke) or death; and clinically significant relapse (palliative systemic therapy initiation >90 days after last trastuzumab dose) or death. Of the 3134 women, 6, 10, and 85 % received 1–8, 9–15, and ≥16 doses, respectively. Over 5-year median follow-up, early trastuzumab discontinuation was associated with more HF/death [1–8 doses hazard ratio (HR) 4.0, 95 % confidence interval (CI) 2.7–6.0; 9–15 doses HR 2.97, 95 % CI 2.1–4.3], non-HF/death (1–8 doses HR 4.3, 95 % CI 3.0–6.1; 9–15 doses HR 3.1, 95 % CI 2.2–4.4), clinically significant relapse/death (1–8 doses HR 3.1, 95 % CI 2.2–4.4; 9–15 doses HR 2.4, 95 % CI 1.8–3.3), and importantly lower OS (77, 80, 93 %; P < 0.001). Early discontinuation (1–8 doses HR 2.41, 95 % CI 1.5–3.8; 9–15 doses HR 2.9, 95 % CI 2.0–4.1) and clinically significant relapse (HR 34.0, 95 % CI 24.9–46.6) were both independent predictors of mortality. Of note, early discontinuation remained a critical independent predictor of OS even after adjusting for incident HF. Early trastuzumab discontinuation is a powerful independent predictor of cardiac events and clinically significant relapse, and both may contribute to poor survival. Both adequate cancer control and optimal CV management are required to improve long-term outcomes.