Abstract PD5-04: NSABP FB-7: A phase II randomized trial evaluating neoadjuvant therapy with weekly paclitaxel (P) plus neratinib (N) or trastuzumab (T) or neratinib and trastuzumab (N+T) followed by doxorubicin and cyclophosphamide (AC) with postoperative T in women with locally advanced HER2-positive breast cancer
Authors: Jacobs SA , Robidoux A , Garcia JMP , Abraham J , La Verde N , Orcutt JM , Cazzaniga ME , Calvo L , Aguirre E , Buyse M , Pogue-Geile KL , Srinivasan A , Song N , Balousek AD , Wolmark N 
Published: May 2016

Abstract
Background:
Trastuzumab (T), the first anti-HER-2-directed therapy, dramatically changed the natural history of operable HER-2 positive breast cancer. A subsequent improvement occurred when pertuzumab was added to a T/docetaxel regimen in NeoSphere, a phase II randomized neoadjuvant trial, in which the pathologic complete response rate (pCR) in breast and nodes was increased from 21.5% to 39.3%, leading to accelerated approval of this combination by the FDA. Another dual anti-HER trial, NeoALTTO, which combined lapatinib with T, resulted in pCR (breast and nodes) increase from 27.6% to 46.8%. Neratinib (N) + paclitaxel (P) followed by AC was tested in the neoadjuvant I-SPY 2 trial resulting in pCR of 55% for hormone-negative, HER2-positive breast cancer. A 300-patient phase III trial of N or T with standard chemotherapy is planned. In the FB-7 phase II trial in HER2-positive patients (pts) with locally advanced disease, pts were randomly assigned to N or T or the combination (N+T) with weekly P followed by standard AC. Arm 3 of this trial, N+T+P, was based on the phase Ib results from NSABP FB-8, a study in heavily pretreated HER2-positive metastatic breast cancer pts, which demonstrated an overall response rate of 38% and clinical benefit rate of 52%.
Methods:
NSABP FB-7 opened in October 2010 as a two-arm trial (Arm 1, N+P→AC and Arm 2, T+P→AC). After accrual of 30 pts, accrual was suspended in December 2011 as NSABP FB-8, a phase Ib trial of neratinib, trastuzumab, and paclitaxel (N+T+P), was conducted and a recommended phase II dose for the combination of N+T+P was determined. NSABP FB-7 reopened in September 2012 adding Arm 3 (N+T+P→AC). 141 pts enrolled in this trial between October 2010 and November 2014. Three withdrew consent before treatment and were replaced. A total of 126 US, Canadian, and European pts were randomized to Arm 1 (N+P→AC), Arm 2 (T+P→AC) or Arm 3 (N+T+P→AC). 12 additional pts from the US were treated on Arm 3 as nonrandomized (NR) pts. These NR pts are included for toxicity but not for efficacy. Eligibility criteria included women &gt;18 years of age, ECOG PS 0-1, stage IIB-IIIC invasive breast cancer, HER2-positivity by IHC 3+, FISH, or CISH as determined by local laboratories, hormone receptor positive or negative, LVEF &gt;50%, and adequate laboratory parameters. The primary endpoint is pCR in breast and nodes.
Conclusions:
The last patient enrolled on this trial in November 2014. Datalock for the primary endpoint will occur on or before September 1, 2015. Pathologic complete response data and toxicity will be reported on the entire cohort of pts. Biomarkers will be analyzed on a subset of pts.
Support: Puma Biotechnology, Inc.
Citation Format: Jacobs SA, Robidoux A, Garcia JMP, Abraham J, La Verde N, Orcutt JM, Cazzaniga ME, Calvo L, Aguirre E, Buyse M, Pogue-Geile KL, Srinivasan A, Song N, Balousek AD, Wolmark N. NSABP FB-7: A phase II randomized trial evaluating neoadjuvant therapy with weekly paclitaxel (P) plus neratinib (N) or trastuzumab (T) or neratinib and trastuzumab (N+T) followed by doxorubicin and cyclophosphamide (AC) with postoperative T in women with locally advanced HER2-positive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD5-04.