Joensuu H, et al. - Researchers determined the influence of administering trastuzumab concomitantly with a taxane for a brief period (9 weeks) on survival outcomes compared to chemotherapy and 1 year of trastuzumab in women with early human epidermal growth factor receptor 2–positive breast cancer. Findings revealed that compared to 1 year of trastuzumab, nine weeks of trastuzumab was not noninferior when given with similar chemotherapy. The 9-week group showed better cardiac safety.

Methods

• Researchers performed an open-label, randomized (1:1) clinical trial including women with HER2-positive breast cancer.
• The 2 groups received identical chemotherapy, consisting of 3 cycles of 3-weekly docetaxel (either 80 or 100 mg/m²) plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide.
• Thereafter, the 9-week group received no trastuzumab, whereas controls received trastuzumab to complete 1 year of administration.
• Comparison of the groups was performed regarding disease-free survival (DFS) using a Cox model and the noninferiority approach.
• For this work, the estimated sample size was 2168 patients (1-sided testing, with a relative noninferiority margin of 1.3).
• They accrued 2176 patients from 7 countries from January 3, 2008, to December 16, 2014.
• DFS was assessed as the primary objective; distant disease–free survival, overall survival, cardiac DFS, and safety were included as secondary objectives.

Results

• Researchers analyzed 2174 women {median age: 56 (interquartile range [IQR], 48-64) years}.
• They followed-up the patients for a median period of 5.2 (IQR, 3.8-6.7) years.
• Findings did not demonstrate noninferiority of the 9-week treatment for DFS (hazard ratio, 1.39; 2-sided 90% CI, 1.12-1.72).
• The groups did not differ significantly in terms of distant disease–free survival and overall survival.
• Cardiac failure was encountered in 36 (3%) and 21 (2%) patients in the 1-year and the 9-week groups, respectively; the 9-week group showed better maintained left ventricle ejection fraction.
• They noted an interaction between the docetaxel dose and DFS; patients in the 9-week group treated with 80 mg/m² displayed inferior and those treated with 100 mg/m² displayed similar DFS as patients in the 1-year group.