Duration of Adjuvant Trastuzumab for HER2-Positive Breast Cancer

Administering 1 year of adjuvant trastuzumab therapy has long been standard clinical practice for patients with human epidermal receptor 2 (HER2)-positive, early-stage breast cancer. This treatment duration was not based on any particular scientific rationale, but rather was agreed upon by committee members who designed the first adjuvant clinical trials of the drug. Initial results of the phase III, international, randomized, open-label HERA trial (Lancet 2007; 369:29) showed that 1 year of adjuvant trastuzumab after standard neoadjuvant or adjuvant chemotherapy conferred a significant overall survival (OS) benefit versus observation at a median follow-up of 2 years in patients with HER2-positive, early-stage, invasive disease. Subsequent data (Lancet Oncol 2013 Jul; 14:741) showed that shorter-duration (6-month) adjuvant trastuzumab did not demonstrate noninferiority versus 1 year of therapy.

Now, to find out if longer-duration therapy confers a benefit, the HERA investigators compared the effectiveness of 2 years versus 1 year of adjuvant trastuzumab at a median follow-up of 8 years in 3105 study patients. The researchers also updated results of 1 year of therapy versus observation in 3399 patients. Patients were randomized to observation alone or 1 or 2 years of adjuvant trastuzumab. The primary endpoint was disease-free survival (DFS).

The same number of DFS events (367) occurred in the 1552 patients receiving trastuzumab for 1 year and the 1553 patients receiving trastuzumab for 2 years. However, grade 3 or 4 adverse events were more common in the 2-year treatment group (20.4% vs. 16.3%), as were decreases in left ventricular ejection fraction (7.2% vs. 4.1%). DFS and overall survival hazard ratios for 1 year of trastuzumab versus observation were 0.76 (P<0.0001) and 0.76 (P=0.0005), despite crossover of 52% of patients from observation to trastuzumab.