Trastuzumab-mediated cardiac dysfunction (CDx) outside of clinical trials: Single Asian center experience

Abstract

e20732 Background: Trastuzumab is an effective drug for the treatment of HER2 positive breast cancer (BC) and CDx has been reported as a major toxicity. The purpose of our study was to investigate the trastuzumab mediated CDx in practice setting and the treatment outcome at single Asian center. Methods: We retrospectively analyzed 181 HER2-overexpressing BC patients (pts) who were treated with trastuzumab containing regimen between January 2005 and December 2007 at Seoul National University Hospital. We investigated the incidence of CDx and the degree of reversibility using echocardiography (EchoCG) and identify the risk factors to predict CDx. Results: Among 181 patients (pts), 112 were treated for palliative purpose and 139 had previously received anthracycline-based chemotherapy. Baseline EchoCG results were available in 129 pts (median age 47; range 25–79) and median left ventricular ejection fraction (LVEF) was 59% (range 45–70). Median follow-up duration was 21 months. LVEF decreased more than 5% points in 37 out of 129 (28.6%). According to the national cancer institute common terminology criteria for adverse events, grade (G) 2 and G 3/4 CDx developed in 4 (3.1%) and 8 (6.2%) pts respectively. Seven pts experienced symptomatic heart failure (HF). 3 among 5 pts who experienced discontinuation of trastuzumab could resume trastuzumab after median 146 (range 94–163) days of discontinuation. Median LVEF was 54% (range 45–63) at baseline in pts who experienced G2–4 CDx and deceased to 45% (range 30–49) after median 175 (range 65–415) days of trastuzumab treatment. HF treatment was initiated in 9 pts. 4 pts received angiotensin converting enzyme inhibitors (ACEI), 3 pts angiotensin receptor blockers (ARB) and 2 pts ACEI or ARB with diuretics. Occurrence of CDx (G2–4) was associated with higher anthracycline cumulative doses (p=0.039) and lower baseline LVEF (p=0.003). The incidence of symptomatic HF was related with past medical history such as hypertension (p=0.019) and lower baseline LVEF (p=0.005). Among the pts who had G2–4 CDx, LVEF was restored to 54% (range 40–59) which was similar to baseline at median 187 (range 56–477) days after the diagnosis of CDx. Conclusions: The majority pts with trastuzumab-mediated CDx were asymptomatic and LVEF could be reversible. No significant financial relationships to disclose.