Assessment of trastuzumab-related cardiac dysfunction in the Herceptin Adjuvant (HERA) Trial with 3.6 years median follow- up

Abstract

540 Background: The Herceptin Adjuvant (HERA) Trial is a three-group randomized trial that compared 1 year or 2 years trastuzumab with observation. We investigated cardiac dysfunction in HERA patients randomized to observation or 1 year trastuzumab and report results at a median follow-up of 3.6 years. Methods: Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF > 55%) were eligible. Cardiac function was monitored throughout the trial. A repeat LVEF assessment was required in case of cardiac dysfunction. Results: There were 1,698 patients randomized to observation and 1,703 randomized to 1 year trastuzumab. The incidence of discontinuation of trastuzumab due to cardiac disorders was low (5.1%). The incidence of cardiac endpoints was low (severe CHF 0.77% in the trastuzumab group). The incidence of cardiac endpoints was higher in the trastuzumab group compared to observation (severe CHF 0.77% vs 0.00%; confirmed significant LVEF drops 3.57% vs 0.64%). In the trastuzumab group, there were no occurrences of severe CHF after the end of the scheduled treatment period of 1 year. Among the patients in the trastuzumab group with confirmed significant LVEF drop, the first occurrence was within the scheduled treatment period of 1 year for 55 out of 60 patients (91.7%). In the trastuzumab group, 59 of 73 patients (80.8%) with a cardiac endpoint reached acute recovery and of these 59 patients 52 (88.1%) were consider to have a favourable long term outcome. Conclusions: The incidence of cardiac endpoints remains low even with longer term follow-up. The cumulative incidence of any type of cardiac endpoint increases during the scheduled treatment period of 1 year, but appears to remain approximately constant after the scheduled treatment period of 1 year is completed. [Table: see text]