Buzdar AU, et al. - Since the pathologic complete response rate (pCR), the primary end point of the American College of Surgeons Oncology Group Z1041 (Alliance) trial, disease-free survival (DFS) and overall survival (OS) in women with operable HER2-positive breast cancer are similar between treatment regimens, researchers evaluated DFS and OS for patients treated with sequential vs concurrent anthracycline plus trastuzumab. They found that, sequential or concurrent administration of FEC (fluorouracil, epirubicin, and cyclophosphamide) with trastuzumab did not offer different pCR, DFS, and OS during a median follow-up of 5.1 years (range, 26 days to 6.2 years).

Methods

• This was a phase 3 randomized clinical trial.
• This trial was conducted at 36 centers in the continental US and Puerto Rico, including women 18 years or older with invasive operable HER2-positive breast cancer enrolled from September 15, 2007 to December 15, 2011, and randomized to 1 of 2 treatment arms.
• On October 15, 2017, the analysis data set was locked, and analysis was completed on December 15, 2017.
• Treatment regimen for patients randomized to arm 1 included receipt of 500 mg/m² of fluorouracil, 75 mg/m²of epirubicin, and 500 mg/m² of cyclophosphamide (FEC) every 3 weeks for 12 weeks followed by the combination of 80 mg/m² of paclitaxel and 2 mg/kg (except initial dose of 4 mg/kg) of trastuzumab weekly for 12 weeks.
• The same combination of paclitaxel with trastuzumab weekly for 12 weeks followed by FEC every 3 weeks with weekly trastuzumab for 12 weeks was administered to the patients randomized to arm 2.
• Endocrine therapy was administered to women with hormone receptor–positive disease, and radiotherapy was delivered at physician discretion.
• DFS and OS and pCR in the breast and nodes were assessed as the primary outcomes.

Results

• In this trial, 282 women with HER2-positive breast cancer were enrolled, and 2 withdrew consent before treatment.
• The remaining 280 women had median age 50 years (range, 28-76 years), with 232 (82.9%) being white, 29 (10.3%) black, 8 (2.9%) Asian, 4 (1.4%) American Indian or Alaskan Native, and 7 (2.5%) not reported race/ethnicity.
• In arm 1 and arm 2, the estimated disease events were 22 and 27, respectively.
• No difference in disease-free survival rates was observed with respect to treatment arm (stratified log-rank P=.96; stratified hazard ratio [HR] [arm 2 to arm 1], 1.02; 95% CI, 0.56-1.83).
• No difference in overall survival was observed with respect to treatment arm (stratified log-rank P=.73; stratified HR [arm 2 to arm 1], 1.17; 95% CI, 0.48-2.88).