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Clinical Trial
. 2019 Jan 1;5(1):45-50.
doi: 10.1001/jamaoncol.2018.3691.

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

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Free PMC article
Clinical Trial

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

Aman U Buzdar et al. JAMA Oncol. .
Free PMC article

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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Meric-Bernstam reported receiving research sponsorship from Genentech, Novartis, Puma Biotechnology, Taiho Oncology, Pfizer, Pieris Pharmaceuticals Inc, and Zymeworks and serving as a consultant for Genentech and Pieris Pharmaceuticals Inc. Dr Royce reported receiving travel and consultancy fees from Syndax; consultancy fees from CellTrion; travel and consultancy fees from Novartis; and grant support to her institution from Novartis. Dr Hunt reported receiving research funding to her institution from Endomagnetics. She serves on advisory boards for Merck and Armada Health. No other disclosures are reported.

Figures

Figure 1.
Figure 1.. CONSORT Diagram
Figure 2.
Figure 2.. Kaplan-Meier Curves for Disease-Free Survival
Figure 3.
Figure 3.. Kaplan-Meier Curves for Overall Survival

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