OT2-01-03: Eribulin in Women with Locally Advanced Breast Cancer Who Do Not Achieve Pathologic Complete Response (pCR) Following Neoadjuvant Chemotherapy: A Sarah Cannon Research Institute Phase II Trial.
Authors: Yardley DA , Peacock NW , Hainsworth JD , Burris III HA 
Published: June 2012

Abstract
Background: Little evidence currently exists to support the use of further therapy for women with localized breast cancer who do not achieve pathologic complete response (pCR) after treatment with standard neoadjuvant chemotherapy. Eribulin is a novel inhibitor of microtubule formation via induction of irreversible cell cycle arrest at G2/M. It retains in vitro activity against cancer cells that are paclitaxel-resistant due to β tubulin mutations, and induces less neuropathy in mice when compared with paclitaxel. Eribulin mesylate was recently approved by the FDA for the treatment of patients with metastatic breast cancer (MBC) who have previously received ≥2 chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.
Study Objectives: This phase II trial is designed to assess the efficacy of eribulin mesylate in women with localized breast cancer who do not achieve pCR following standard neoadjuvant chemotherapy (+ trastuzumab in HER2−positive tumors). The primary endpoint is 2-year disease-free survival (DFS). The secondary goal of this trial is to assess the feasibility of the administration of 6 post-operative cycles of eribulin in patients (pts) who have received neoadjuvant chemotherapy.
Eligibility: Women aged ≥18 years with a histological diagnosis of invasive breast cancer (T1-3, N1-2, M0) who have received ≥4 cycles of anthracycline and/or taxane containing neoadjuvant chemotherapy regimen (+trastuzumab in HER2−positive tumors) are eligible. Pts must have failed to achieve a pCR following neoadjuvant treatment (i.e. residual invasive breast cancer (&gt;5mm) in the breast or lymph nodes at surgery [ypT1b-T4, N1-N2, M0]). Additional eligibility criteria include: ECOG performance status of 0–1; adequate hematologic, hepatic and renal function. Pts with nonhealed surgical wounds, known or active cardiovascular disease, QTc interval &gt; 480 msecs, chronic use of QTc prolonging drugs, as well as previous breast cancer diagnosis &lt;3 years prior to trial entry, are excluded.
Trial Design: Pts are stratified into three cohorts according to HER2 and hormone receptor status as follows: triple-negative (Cohort A, n=54), hormone-receptor positive/HER2−negative (Cohort B, n=42) and HER2−positive (Cohort C, n=52). All pts receive eribulin mesylate 1.4mg/m2 IV on days 1&8 of each 21-day treatment cycle for 6 cycles. Pts with HER2−postive tumors also receive trastuzumab 6mg/kg IV day 1 of each cycle. Locoregional radiotherapy and/or adjuvant hormonal therapy (Cohort B only) will be administered per institutional guidelines. With standard neoadjuvant therapy, the approximate 2-year DFS of pts who do not achieve pCR are as follows: triple-negative, 40%; hormone-receptor-positive/HER2−negative, 80%; and HER2−positive, 60%. For a one-sided test of hypothesis at alpha = 0.10 and power = 0.80, the required numbers of evaluable patients treated in each cohort are 49, 38, and 47, respectively, to demonstrate improvement in treatment outcome in these groups of at-risk pts.
The trial is currently enrolling and has an accrual goal of 148 patients.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-01-03.