Abstract OT3-3-08: Eribulin/Cyclophosphamide versus Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Locally Advanced HER2-Negative Breast Cancer: A Randomized Phase II Trial of the Sarah Cannon Research Institute
Authors: Yardley DA , Hainsworth JD , Shastry M , Finney L , Burris HA 
Published: August 2014

Abstract
Background: Neoadjuvant chemotherapy for locally advanced breast cancer improves survival and rates of breast-conserving surgery. Pathologic complete response (pCR) after neoadjuvant therapy strongly correlates with improved disease free survival (DFS) and provides an early indicator of treatment efficacy. The expected pCR rate with a standard taxane-containing combination is approximately 18%. Eribulin is a non-taxane synthetic analogue of halichondrin B that inhibits microtubule dynamics by a novel mechanism of action distinct from other tubulin-targeting agents. Eribulin is active against taxane and anthracycline pretreated metastatic breast cancer (MBC) and is well tolerated with a predictable toxicity profile. Substitution of eribulin for docetaxel in a neoadjuvant combination regimen may therefore improve efficacy. This study will evaluate the non-anthracycline eribulin/cyclophosphamide (ErC) and docetaxel/cyclophosphamide (TC) combinations as neoadjuvant therapy. The first ten patients (pts) will be evaluated for tolerability and feasibility of standard prescribed eribulin monotherapy dosing in combination with standard dose cyclophosphamide.
Study Objectives: This randomized phase II trial is designed to determine the pCR rate of locally advanced, HER2-negative breast cancer treated with 6 cycles of ErC or TC. The secondary objectives are to evaluate the clinical response rate of ErC as neoadjuvant therapy and to determine the 2 year DFS of pts treated with ErC and TC.
Eligibility: Females ≥ 18 years with untreated, locally advanced, HER2-negative breast cancer appropriate for neoadjuvant chemotherapy are eligible. Eligibility criteria include: adenocarcinoma histology; clinical T1-3, N0-2, M0 breast tumors; ECOG PS 0–2; known hormone receptor status at study entry; adequate bone marrow and organ function; willingness to provide archived biopsy specimen for correlative testing. Clinical N3, T1N0M0, and T4 tumors are excluded. Upfront axillary lymph node sampling and/or definitive nodal surgery is permitted, and demonstrated pN3a disease is allowed.
Trial Design: A lead-in phase of the trial will enroll 10 pts to be treated with ErC to determine safety and feasibility of the combination. If the safety is confirmed, subsequent pts will be stratified by hormone receptor status (positive vs. triple- negative) and will be randomized in a 2:1 ratio to Arm 1: ErC or Arm 2: TC. Pts on Arm 1 will receive eribulin 1.4 mg/m2 IV (Days 1 & 8) and cyclophosphamide 600 mg/m2 IV (Day 1). Pts on Arm 2 will receive docetaxel 75 mg/m2 IV (Day 1) and cyclophosphamide 600 mg/m2 IV (Day 1). Both regimens are repeated every 21 days for a total of 6 cycles. After completion of neoadjuvant chemotherapy, pts will undergo definitive local surgery, as determined by the treating surgeon. Archival tumor samples and residual tumor tissue at surgery will be collected for biomarker evaluations. A total of 66 pts (Arm 1: 44; Arm 2: 22) will be enrolled to this study. A pCR rate ≥ 18% in patients treated with ErC is considered a study result that merits further evaluation. This trial is pending activation and has a total accrual goal of 76 pts.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-3-08.