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Original Investigation
January 2019

Disease-Free and Overall Survival Among Patients With Operable HER2-Positive Breast Cancer Treated With Sequential vs Concurrent Chemotherapy: The ACOSOG Z1041 (Alliance) Randomized Clinical Trial

Author Affiliations
  • 1Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston
  • 2Department of Health Sciences Research, Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota
  • 3Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston
  • 4Department of Surgery, University of Texas Southwestern Medical Center, Dallas
  • 5Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas
  • 6Department of Surgery, Mayo Clinic, Rochester, Minnesota
  • 7Doctor’s Hospital of Laredo, Laredo, Texas
  • 8Department of Medical Oncology, University of New Mexico School of Medicine, Albuquerque
  • 9Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston
JAMA Oncol. 2019;5(1):45-50. doi:10.1001/jamaoncol.2018.3691
Key Points

Question  What are the long-term outcomes associated with 2 different approaches to administering trastuzumab with neoadjuvant chemotherapy in patients with HER2-positive breast cancer?

Findings  Analysis of the ACOSOG Z1041 (Alliance) study of 280 patients revealed no difference in disease-free or overall survival for patients given a regimen of paclitaxel plus trastuzumab followed by fluorouracil, epirubicin, and cyclophosphamide plus trastuzumab compared with a regimen of fluorouracil, epirubicin, and cyclophosphamide followed by paclitaxel plus trastuzumab.

Meaning  Across a median follow-up of 5 years, no differences were found in disease-free or overall survival between the 2 approaches of administering trastuzumab with neoadjuvant chemotherapy in patients with HER2-positive breast cancer.

Abstract

Importance  Pathologic complete response rate (pCR), the primary end point of the ACOSOG (American College of Surgeons Oncology Group) Z1041 (Alliance) trial, and disease-free survival (DFS) and overall survival (OS) in women with operable HER2-positive breast cancer are similar between treatment regimens.

Objective  To assess DFS and OS for patients treated with sequential vs concurrent anthracycline plus trastuzumab.

Design, Setting, and Participants  Phase 3 randomized clinical trial conducted at 36 centers in the continental United States and Puerto Rico. Women 18 years or older with invasive operable HER2-positive breast cancer were enrolled from September 15, 2007, to December 15, 2011, and randomized to 1 of 2 treatment arms. The analysis data set was locked on October 15, 2017, and analysis was completed on December 15, 2017.

Interventions  Patients randomized to arm 1 received 500 mg/m2 of fluorouracil, 75 mg/m2 of 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. Patients randomized to arm 2 received the same combination of paclitaxel with trastuzumab weekly for 12 weeks followed by FEC every 3 weeks with weekly trastuzumab for 12 weeks. Women with hormone receptor–positive disease received endocrine therapy, and radiotherapy was delivered at physician discretion.

Main Outcomes and Measures  The primary outcomes were DFS and OS and pCR in the breast and nodes.

Results  Two hundred eighty-two women with HER2-positive breast cancer were enrolled in the trial, and 2 withdrew consent before treatment. Among the remaining 280 women, the median age was 50 years (range, 28-76 years), 232 (82.9%) were white, 29 (10.3%) were black, 8 (2.9%) were Asian, 4 (1.4%) were American Indian or Alaskan Native, and 7 (2.5%) did not report race/ethnicity. There were 22 disease events in arm 1 and 27 in arm 2. Disease-free survival rates did not differ 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). Overall survival did not differ 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).

Conclusions and Relevance  Across a median follow-up of 5.1 years (range, 26 days to 6.2 years), pCR, DFS, and OS did not differ with respect to sequential or concurrent administration of FEC with trastuzumab.

Trial Registration  ClinicalTrials.gov identifier: NCT00513292

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