Abstract OT2-2-03: MERIBEL study: Efficacy of eribulin in first line of taxane-resistant patients with HER2 negative metastatic breast cancer
Authors: Ortega Vanessa , Martínez María , Antón Antonio , Garau Isabel , Calvo Lourdes , Blanco Esperanza , Fernández Yolanda , Illarramendi José Juan , García Mirta , Llombart Antonio , Cortés Javier 
Published: May 2015

Abstract
Brief background discussion:
Eribulin is a nontaxane microtubule dynamics inhibitor. It has shown a significant benefit in overall survival in patients with metastatic breast cancer (MBC) that underwent treatments in multiple previous lines (Cortes et al. 2009). However, little is known about the activity of the drug in patients with taxane-resistant early advanced disease. This trial is designed to determine the safety and efficacy of Eribulin as single first line agent in the treatment of patients with HER2(-) MBC deemed resistant to taxanes.
Trial design:
This study is a Phase IIa, multicenter, open-label, single-arm in patients with HER2 (-) metastatic breast cancer clinical trial. The scheme consists in the administration of 1,23 mg/m2 of Eribulin (equivalent to 1.4mg/m2 eribulin mesylate) as single agent the days 1 and 8 of each 21 days of the cycle, until progression of illness, unacceptable toxicity level or investigator’s criteria. The study was approved by the competent authorities and Ethics committees from 14 participating centers in Spain and Portugal.
Eligibility criteria:
The principal inclusion and exclusion criteria were: (1) Patients with MBC that have not received prior chemotherapy for Advanced disease; (2) Previous chemotherapy for early stages (I-IIIB) including taxanes (paclitaxel and/or docetaxel) for at least 4 cycles; (3) Less than 36 months* between the last cycle with taxanes and metastatic relapse; (4) Evaluable disease under RECIST criteria; (5) Absence of HER2 over-expression (IHQ of 0/1 or negative FISH/CISH); (6) Absence of neurotoxicity &gt; G1.
(*) Amended to 48 months (Llombart et al. ASCO 2013).
Specific aims:
The main objective is to determine the efficacy of Eribulin as single first line agent in the treatment of patients with HER2-negative MBC and taxanes resistant criteria. Secondary objectives are: Estimate the tolerance to the treatment; assess the clinical response of the study treatment by RECIST criteria; correlate hormone receptor status (+/-) with clinical response and tolerability; identify the relationship between presence of visceral disease and response to therapy.
Statistical Methods:
The primary endpoint is time to progression (TTP). Secondary endpoints include the safety of treatment, clinical benefit rate, objective response, progression-free survival and overall survival.
A total of 60 patients were predefined for the primary outcome. The sample size is based on a one-arm survival design. We test the null hypothesis that true TTP is 3.7 versus the alternative hypothesis (H1) that TTP is 5.5 months. An interim analysis with 30 patients completed has been planned. The study will be stopped for futility or efficacy if conditional power is less than 20% or more than 80%, respectively. Type I and II error assumed were 5% one-sided and 16%, respectively.
Present accrual:
Currently, 16 women have been recruited for the trial since study start in July 2013. The expected end of accrual will be on March 2015.
Contact information for people with a specific interest in the trial:
Maria Campos (maria.campos@medsir.org)
Scientific director
Medica Scientia Innovation Research (MedSIR ARO).
Citation Format: Vanessa Ortega, María Martínez, Antonio Antón, Isabel Garau, Lourdes Calvo, Esperanza Blanco, Yolanda Fernández, José Juan Illarramendi, Mirta García, Antonio Llombart, Javier Cortés. MERIBEL study: Efficacy of eribulin in first line of taxane-resistant patients with HER2 negative metastatic breast cancer [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 OT2-2-03.