ACOSOG Z1041 (Alliance): Definitive analysis of randomized neoadjuvant trial comparing FEC followed by paclitaxel plus trastuzumab (FEC → P+T) with paclitaxel plus trastuzumab followed by FEC plus trastuzumab (P+T → FEC+T) in HER2+ operable breast cancer.

Breast Cancer - HER2/ER
Session Type and Session Title: 
Oral Abstract Session, Breast Cancer - HER2/ER
Abstract Number: 



J Clin Oncol 31, 2013 (suppl; abstr 502)


Aman Buzdar, Vera J. Suman, Funda Meric-Bernstam, A. Marilyn Leitch, Matthew James Ellis, Judy Caroline Boughey, Gary Walter Unzeitig, Melanie Royce, Kelly Hunt, for the Alliance for Clinical Trials in Oncology; The University of Texas MD Anderson Cancer Center, Houston, TX; ACOSOG Statistical Center, Mayo Clinic, Rochester, MN; Simmons Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO; Mayo Clinic, Rochester, MN; Doctors Hospital of Laredo, Laredo, TX; University of New Mexico Cancer Center, Albuquerque, NM

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: Neoadjuvant chemotherapy (NAC) and concomitant trastuzumab (T) have produced high pathologic complete response (pCR) rates in HER2+ breast cancers. Z1041 addresses the timing of initiation of T with NAC. Methods: Women with operable HER2+ invasive breast cancer were randomized 1:1 to: FEC → P+T (Arm 1) or P+T → FEC+T (Arm 2) where treatment was administered as 5-FU 500 mg/m2, epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 day 1 of a 21-day cycle x 4 (FEC); paclitaxel 80 mg/m2 weekly x 12 and trastuzumab 4 mg/kg once then 2 mg/kg weekly x 11. Eligibility also included: tumor > 2 cm or a positive lymph node and left ventricular ejection fraction > 55%. The primary aim was to compare the pCR rates in the breast (pBCR) between the regimens. Secondary endpoints were pCR rate in the breast and lymph nodes (pBNCR) and safety profile. All pts who began study treatment were included in the analyses. With 128 pts per regimen, a two-sided alpha=0.05 test of proportions would have a 90% chance of detecting a difference of 20% or more in the pBCR rates, when the pBCR rate with the poorer regimen is ≤ 25%. Results: From September 15, 2007 to December 15, 2011, 282 women (Arm 1: 140 pts) were enrolled. Two pts (Arm 1) withdrew without receiving treatment. The two arms were similar in age, stage, and hormone receptor (HR) status (HR neg: 40%). The severe (grade 3+) treatment-related toxicities included: neutropenia (Arm 1: 24.6%; Arm 2: 32.4%), fatigue (Arm 1: 4.3%; Arm 2: 8.5%), and neurosensory problems (Arm 1: 3.6%; Arm 2: 4.9%). The pBCR rate and pBNCR rates (Table) were not found to differ between the two regimens (Fisher’s exact p values: 0.905 and 0.811, respectively). Conclusions: High pCR rates can be achieved with trastuzumab in combination with anthracyclines and taxanes. The pBCR or pBNCR was not different between regimens based on the timing of initiation of trastuzumab. Clinical trial information: NCT00513292.

n 138 142
% pCR in breast
(95% CI)
46.4- 63.5
% pCR in breast and nodes
(95% CI)
42.1 – 59.3