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Sequential vs Concurrent Neoadjuvant Therapy in HER2-Positive Breast Cancer

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Key Points

  • No signifcant difference in pathologic complete response between sequential and concurrent trastuzumab and FEC was observed in the trial.
  • No difference in disease-free or overall survival was observd over 5 years of follow-up.

As reported in JAMA Oncology by Buzdar et al, the phase III ACOSOG Z1041 (Alliance) trial showed no difference in disease-free or overall survival with sequential vs concurrent neoadjuvant anthracycline and trastuzumab in patients with operable HER2-positive breast cancer. An earlier report from the trial showed no difference in pathologic complete response rates—the study’s primary endpoint—with sequential vs concurrent treatment.

Study Details

The open-label trial included 280 patients from 36 sites in the United States and Puerto Rico between September 2007 and December 2011. Participants were randomized to receive either:

  • 500 mg/m2 of fluorouracil, 75 mg/m2 of epirubicin, and 500 mg/m2 of cyclophosphamide (FEC) on day 1 of 21-day cycles for 4 cycles, followed by four 21-day cycles of 80 mg/m2 of paclitaxel plus trastuzumab (4 mg/kg initial dose, 2 mg/kg for subsequent doses) on days 1, 8, and 15 (sequential group, n = 138)
  • 80 mg/m2 of paclitaxel plus trastuzumab (4 mg/kg initial dose, 2 mg/kg for subsequent doses) on days 1, 8, and 15 of a 21-day cycle for 4 cycles, followed by four 21-day cycles of FEC on day 1 plus 2 mg/kg of trastuzumab on days 1, 8, and 15 (concurrent group, n = 142).

After surgery, patients received 6 mg/kg of trastuzumab every 3 weeks, to complete a total of 52 weeks of treatment from the first preoperative dose. Patients with hormone receptor–positive disease received endocrine therapy, and radiotherapy was delivered at physician discretion.

The data set for the current analysis was locked in October 2017. Differences between the groups in disease-free and overall survival were assessed by stratified log-rank test, with strata consisting of age (younger than 50 years vs not), hormone receptor profile, and clinical tumor stage.

Disease-Free and Overall Survival

Median follow-up was 5.1 years. Overall, 22 disease events occurred in the sequential group and 27 occurred in the concurrent group (stratified hazard ratio [HR] for concurrent vs sequential = 1.02, P = .96).  Overall, 8 deaths occurred in the sequential group and 12, in the concurrent group (stratified HR for concurrent vs sequential = 1.17, P = .73).

The investigators concluded, “An earlier report of the results of the Z1041 phase III trial compared the [pathologic complete response] of patients with HER2-positive breast cancer treated with FEC followed by paclitaxel and trastuzumab with that of patients treated with paclitaxel and trastuzumab followed by FEC and trastuzumab. Pathologic complete response rates did not differ with respect to concurrent or sequential administration of trastuzumab with FEC. Herein we report, with a median follow-up of 5.1 years, that the [disease-free and overall survival] also did not differ with respect to concurrent or sequential administration of trastuzumab with FEC. Therefore, concurrent administration of trastuzumab with FEC was not found to offer additional clinical benefit and is not warranted.”

The study was supported by grants and awards from the National Cancer Institute.

Kelly K. Hunt, MD, of the Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author of the JAMA 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®.


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