At a median follow-up of 8 years, patients receiving trastuzumab (Herceptin) sequentially after chemotherapy and radiotherapy in the Herceptin Adjuvant (HERA) trial had a low incidence of cardiac events and these were reversible in the vast majority of patients. This long-term assessment confirms and extends previous reports of cardiac safety.
The three-arm HERA trial compared 2 years or 1 year of trastuzumab with observation in 5,102 patients with human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer. “This is the first time that results of the 2-year trastuzumab arm have been reported, and the follow-up time has doubled,” researchers reported in the Journal of Clinical Oncology.
Eligible patients had a left-ventricular ejection fraction of at least 55% following neoadjuvant chemotherapy with or without radiotherapy and cardiac function was closely monitored. Cardiac adverse events leading to discontinuation of trastuzumab occurred in 9.4% of the 1,673 patients receiving 2 years of trastuzumab and 5.2% of the 1,682 patients receiving 1 year of trastuzumab.
Cardiac death, severe congestive heart failure, and confirmed significant left-ventricular ejection fraction decrease remained low in both treatment and the observation arms. “The incidence of severe [congestive heart failure] (0.8%, 0.8%, and 0.0%, respectively) and confirmed significant [left-ventricular ejection fraction] decrease (7.2%, 4.1%, and 0.9%, respectively) was significantly higher in the 2-year and 1-year trastuzumab arms compared with the observation arm. Severe [congestive heart failure] was the same for 2-year and 1-year trastuzumab,” the investigators stated. More than 80% of patients with confirmed left-ventricular ejection fraction decrease receiving trastuzumab for 1 or 2 years reached acute recovery, defined as two or more sequential left-ventricular ejection fraction assessments of > 50%.
“Importantly, our data are consistent with the reassuring cardiac safety data reported in the other pivotal adjuvant trastuzumab trials testing the 1-year trastuzumab duration,” the authors noted. This includes the NSABP B-31 trial, which reported a 4.0% incidence of cardiac events in the trastuzumab arm vs 1.3% in the control arm, with most of those experiencing a cardiac event recovering within 6 months.
“Despite this low incidence of cardiac toxicity in our trial, patients treated with adjuvant trastuzumab should have a cardiac assessment before and during its administration to ensure the early detection of cardiac events and prompt treatment,” the authors advised. ■
de Azambuja E, at al: J Clin Oncol. June 9, 2014 (early release online).