Abstract P3-11-08: Eribulin/cyclophosphamide (ErC) versus docetaxel/cyclophosphamide (TC) as neoadjuvant therapy in locally advanced HER2-negative breast cancer: A randomized phase II trial of the Sarah Cannon Research Institute
Authors: Yardley Denise , Dyehouse Karyn , Mani Aruna , Calfa Carmen , Drosick David , Yost Kathleen , Shipley Diana , Quinn Raven , Young Robyn , Finney Lindsey , Earwood Chris , Shastry Mythili , Hainsworth John 
Published: May 2015

Abstract
Background: Pathologic complete response (pCR) following neoadjuvant chemotherapy for locally advanced breast cancer strongly correlates with improved disease-free survival, rates of breast-conserving surgery, and provides an early indicator of treatment efficacy. Standard taxane-containing neoadjuvant combinations result in pCR rates of 18% in unselected patient (pt) populations. Eribulin (Er) is a novel inhibitor of microtubule dynamics. In the EMBRACE trial, Er demonstrated a survival advantage in anthracycline and taxane pretreated breast cancer. This study evaluated non-anthracycline regimens of Er in combination with cyclophosphamide (ErC) and docetaxel/cyclophosphamide (TC) as neoadjuvant therapy in HER2-negative breast cancer.
Methods: Adult women with histologically confirmed invasive HER2-negative (defined as IHC 0-1+ or FISH/SISH negative), clinical stage T1-3, N0-2, M0 (pN3a disease allowed) adenocarcinoma of the breast were eligible. Additional eligibility criteria included: ECOG PS 0,1 or 2; normal cardiac function, known hormone receptor status for stratification; adequate hematologic, liver, and renal function. Following a 10 pt lead-in to confirm the safety and feasibility of ErC, pts were randomized in a 2:1 ratio: Arm 1, Er 1.4 mg/m2 IV (Days 1 & 8) and C 600 mg/m2 IV (Day 1); Arm 2, T 75 mg/m2 IV and C 600 mg/m2 IV on Day 1, both regimens administered q 21 days x 6 cycles followed by surgery. Locoregional radiation and/or antiestrogen therapy were prescribed postoperatively according to standard guidelines. Tumor samples were collected at baseline and from residual disease noted at the time of surgery. A pCR rate ≥18% in pts treated with ErC warranted further evaluation.
Results: Enrollment was completed April 2014 (76 pts); 66 pts were randomized (Arm 1, 44; Arm 2, 22). Median age was 52 years (range, 23-77); 88% ECOG 0; 79% invasive ductal adenocarcinoma; median baseline primary tumor size 3cm (range, 0.4-10cm; 30% were T3); axillary nodes clinically positive in 51%. Thirty-three percent were triple negative. 55 pts (72%) received neoadjuvant therapy and underwent surgery. 16 pts continue to receive study treatment. At this time, pts who underwent surgery have similar pCR rates with ErC and TC (14%, 5/37 vs. 11%, 2/18 respectively). 3 of 51 hormone receptor positive pts (6%) and 4 of 25 triple negative pts (16%) had pCR. Neutropenia (40%) was the most common grade 3/4 toxicity. Common treatment-related toxicities included: fatigue (66%), alopecia (57%), and nausea (54%). Peripheral neuropathy incidence is currently lower with ErC than with TC (30% vs 45%) with 3 grade 3 events on TC. Prophylactic growth factor use was higher in TC than with ErC (77% vs 24%).
Conclusions: Eribulin in combination with cyclophosphamide was well tolerated with no unexpected toxicities. At present, pCR rates with both regimens are within the range previously reported with docetaxel/cyclophosphamide and other standard taxane-containing neoadjuvant regimens. Final efficacy and toxicity data will be presented. A planned exploratory correlative tissue analysis may identify tumors more likely to derive benefit from eribulin-based therapies.
Citation Format: Denise Yardley, Karyn Dyehouse, Aruna Mani, Carmen Calfa, David Drosick, Kathleen Yost, Diana Shipley, Raven Quinn, Robyn Young, Lindsey Finney, Chris Earwood, Mythili Shastry, John Hainsworth. Eribulin/cyclophosphamide (ErC) versus docetaxel/cyclophosphamide (TC) as neoadjuvant therapy in locally advanced HER2-negative breast cancer: A randomized phase II trial of the Sarah Cannon Research Institute [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-11-08.