Cardiac toxicity and adjuvant trastuzumab for breast cancer – the Cancer Centre of Southeastern Ontario experience.

Abstract

Abstract Abstract #3158 Background: In May 2005 several large randomized trials reported a significant improvement in DFS following the addition of trastuzumab (T) to adjuvant chemotherapy (CT) in early stage breast cancer (BC) such that in the summer of 2005 adjuvant T became standard of care for patients (pts) whose tumors over-expressed her2. Cardiotoxicity had been reported as the main toxicity suffered by pts exposed to T. As the generalizability of clinical trial results to the 'real world' is under increasing scrutiny from the oncology community, we undertook this study to identify and follow the population of interest and to characterize cardiac toxicity related to adjuvant T as practice changed.
 Methods: We conducted a retrospective review of electronic and paper records of all pts prescribed adjuvant T for early stage BC at the Cancer Centre of Southeastern Ontario from June 2005 through January 2007; collecting demographic, disease-related, and treatment-related variables, along with serial left ventricular ejection fraction (LVEF) measurements for each pt.
 Results: 54 pts prescribed adjuvant T were identified in this time period, nearly half of which were still on T at the time of this analysis. Mean age was 54.4 ± 9.5 years, 38.9% had N0 disease, and 40.7% had left sided tumors, with 42.6% being ER+ and 50% being PR+. Most pts received anthracycline based CT (53.7%) and 39% received an anthracycline/taxane combination. T was concurrently with CT in 14.8% of pts, concurrently with radiotherapy in 33.3% and sequentially in the remainder. T was initiated at a mean of 91.2 days from completion of chemotherapy (range 19-365). Our local protocol mandated LVEF assessments at baseline pre CT, upon completion of CT and/or prior to initiation of T for all pts, and while on T all pts underwent LVEF assessments at 12, 24, 36, 48 and 52 weeks, and in response to any symptoms suggesting cardiac dysfunction. Mean LVEF pre CT and post CT was 64% and 62% respectively. We saw no change in LVEF post CT and pre T. We noted a significant decline in LVEF after 12 weeks on T, from 60.5 ± 6.2% to 56.5 ± 9.5% respectively (p = 0.003), with LVEF values remaining stable thereafter. However, at the time of this analysis only approximately half the pts had completed the full year of therapy. Twelve pts (22.2%) interrupted their T therapy due to a drop in LVEF of >10%, only one pt experienced symptomatic cardiotoxicity requiring treatment. Of these twelve, only two pts restarted T at a later date. Follow-up of those patients still on trastuzumab is ongoing.
 Discussion: Adjuvant trastuzumab in general clinical practice is associated with significant decreases in LVEF that are associated with premature discontinuation of therapy. A better understanding of factors associated with LVEF decline and the trends in LVEF over time may allow for targeted interventions for pts at risk. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3158.