HERA Trial 8-Year Follow-up Shows Low Rate of Trastuzumab-Associated Cardiac Dysfunction
In a study reported in Journal of Clinical Oncology, Azambuja et al found low rates of trastuzumab (Herceptin)-related cardiac dysfunction over a median of 8 years of follow-up in the HERceptin Adjuvant (HERA) trial. The majority of patients with cardiac dysfunction achieved acute recovery.
Study Details
In the HERA trial, 5,102 patients with HER2-positive early-stage breast cancer were randomly assigned to receive trastuzumab for 1 or 2 years or observation. Patients had to have left-ventricular ejection fraction ≥ 55% after surgery and neoadjuvant or chemotherapy with or without radiotherapy. The current analysis included 1,673 patients who received 2 years of trastuzumab, 1,682 who received 1 year of trastuzumab, and 1,744 who were assigned to observation.
Cardiac events leading to discontinuation of trastuzumab occurred in 9.2% of patients in the 2-year group and 5.2% in the 1-year group.
Cardiac Events During Follow-up
During follow-up, cardiac death occurred in 0.2% of patients in the 2-year group (difference vs observation = 0.1%, 95% confidence interval [CI] = –0.2 to 0.3), 0% of the 1-year group (difference vs observation = –0.1%, 95% CI = –0.3 to 0.0), and 0.1% of the observation group. Severe congestive heart failure occurred in 0.8% of the 2-year group (difference vs observation = 0.8%, 95% CI = 0.4–1.2), 0.8% of the 1-year group (difference vs observation = 0.8%, 95% CI = 0.4–1.3), and 0% of the observation group.
Confirmed significant decrease in left-ventricular ejection fraction (absolute decrease of at least 10 percentage points from baseline and to < 50%) occurred in 7.2% of the 2-year group (difference vs observation = 6.3%, 95% CI = 5.0–7.6), 4.1% of the 1-year group (difference vs observation = 3.2%, 95% CI = 2.2–4.3), and 0.9% of the observation group. The difference between the 2-year group and the 1-year group was significant (difference = 3.1%, 95% CI = 1.5–4.6, P < .001).
Acute Recovery Rates
In the 2-year patients with any cardiac endpoint, 87.2% reached acute recovery, with median time to recovery of 7.2 months. After median observation of 72.5 months in those with acute recovery, 34.5% had subsequent left-ventricular ejection fraction decrease to < 50%. In the 1-year patients with any cardiac endpoint, 79.5% reached acute recovery, with median time to recovery of 6.6 months. After median observation of 77.8 months in these patients, 37.9% had subsequent decrease in left-ventricular ejection fraction to < 50%.
Among patients with confirmed significant left-ventricular ejection fraction decrease, acute recovery was reached in 87.5% of 2-year patients and 81.2% of 1-year patients, with subsequent decrease in left-ventricular ejection fraction to < 50% occurring in 34.3% and 37.5%.
The investigators concluded, “Long-term assessment at 8-year median follow-up confirms the low incidence of cardiac events for trastuzumab given sequentially after chemotherapy and radiotherapy, and cardiac events were reversible in the vast majority of patients.”
Evandro de Azambuja, MD, PhD, of the Jules Bordet Institute, Brussels, is the corresponding author for the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
