Adjuvant trastuzumab for 1 or 2 years resulted in low but significantly higher rates of severe CHF (0.8% vs 0.0%) and significant LVEF decrease (4.1% and 7.2% vs 0.9%) compared with observation.
RCT (n=5,102)
three-arm
Does 1 or 2 years of trastuzumab increase the risk of cardiac dysfunction in patients with HER2-positive early-stage breast cancer compared to observation?
At 8 years of follow-up, trastuzumab-associated cardiac events in early-stage breast cancer patients remain low and are largely reversible.
Absolute Event Rate: 4.1% vs 0.9%
PURPOSE: To document the rate and outcome of trastuzumab-associated cardiac dysfunction in patients following 1 or 2 years of adjuvant therapy. PATIENTS AND METHODS: The Herceptin Adjuvant (HERA) trial is a three-arm, randomized trial comparing 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. Cardiac function was closely monitored. Eligible patients had left ventricular ejection fraction (LVEF) ≥ 55% at study entry following neoadjuvant chemotherapy with or without radiotherapy. This 8-year median follow-up analysis considered patients randomly assigned to 2 years or 1 year of trastuzumab or observation. RESULTS: The as-treated safety population for 2 years of trastuzumab (n = 1,673), 1 year of trastuzumab (n = 1,682), and observation (n = 1,744) is reported. Cardiac adverse events leading to discontinuation of trastuzumab occurred in 9.4% of patients in the 2-year arm and 5.2% of patients in the 1-year arm. Cardiac death, severe congestive heart failure (CHF), and confirmed significant LVEF decrease remained low in all three arms. The incidence of severe CHF (0.8%, 0.8%, and 0.0%, respectively) and confirmed significant LVEF 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 CHF was the same for 2-year and 1-year trastuzumab. Of patients with confirmed LVEF decrease receiving 2-year trastuzumab, 87.5% reached acute recovery. Of patients with confirmed LVEF decrease receiving 1-year trastuzumab, 81.2% reached acute recovery. CONCLUSION: 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.
Azambuja et al. (Tue,) conducted a rct in HER2-positive early-stage breast cancer (n=5,102). trastuzumab vs. observation was evaluated on confirmed significant LVEF decrease. Adjuvant trastuzumab for 1 or 2 years resulted in low but significantly higher rates of severe CHF (0.8% vs 0.0%) and significant LVEF decrease (4.1% and 7.2% vs 0.9%) compared with observation.