Abstract OT2-09-01: A multicenter, randomized, phase II trial evaluating the efficacy of eribulin monotherapy and eribulin plus endocrine therapy in locally-recurrent or metastatic breast cancer patients after progression on endocrine therapy (REVERT study)
Authors: Pérez-García José Manuel , Salgado Alfonso Cortés , Miranda Elena López , Antón Antonio , Rovira Pedro Sánchez , Fernández Beatriz Castelo , González Ana López , Garau Isabel , Martínez Alejandro , Aparicio Miguel Corbellas , Barco Sonia Del , Sampayo Miguel , Riva François , Malfettone Andrea , Llombart-Cussac Antonio , Cortés Javier 
Published: March 2020

BACKGROUND: Previous studies have shown prolonged overall survival (OS) in patients with metastatic breast cancer (MBC) treated with eribulin, without a clear improvement in progression-free survival (PFS), which might indicate an eribulin-mediated suppression of further spread of metastasis. In addition, it was shown that 44.1% of patients with luminal B-like tumors who received neoadjuvant eribulin converted to the luminal A-like subtype, which might be associated to a more endocrine-sensitive behavior. The aim of this trial is to explore the efficacy of eribulin in combination with the same drug administered in the last endocrine therapy (ET) regimen in hormone receptor (HR)-positive (+) / human epidermal growth factor receptor 2 (HER2)-negative (-), locally-recurrent or MBC patients who had previously shown progression while on an aromatase inhibitor (AI)-containing regimen in the metastatic setting or within six months from their last AI dose in the adjuvant setting. TRIAL DESIGN: This is an open-label, randomized, multicenter phase II trial. Patients will be randomized 1:1 to receive either eribulin alone (Arm A) or eribulin in combination with the last AI administered either in the metastatic or adjuvant setting (Arm B). Patients will receive eribulin intravenously on days 1 and 8 of every 21-day cycle, alone or in combination with exemestane, letrozole, or anastrozole, until disease progression or unacceptable toxicity. Main selection criteria are: (1) Pre- or post-menopausal women, who received an AI +/- gonadotropin-releasing hormone analogue in the last ET regimen; (2) HR+ / HER2-, unresectable locally advanced or MBC; (3) Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria v. 1.1; (4) At least one taxane or anthracycline regimen in either the neoadjuvant or adjuvant setting; (5) Patients with no prior line of chemotherapy in the metastatic setting; (6) At least 1 and up to 3 prior lines of ET in the metastatic setting. The primary objective of the study is to assess the overall response rate (ORR) in treatment Arm B, defined as the proportion of patients with confirmed complete or partial response according to the RECIST criteria v.1.1. Secondary objectives include: (1) PFS, PFS-2, OS, clinical benefit rate, duration of response, change in maximum tumor shrinkage in both arms, and ORR in Arm A; (2) Safety-related outcome as per Common Terminology Criteria for Adverse Events v. 5.0. Patients will be accrued in a Simon’s two-stage admissible design. In stage I, the accrual goal will be a total of 22 patients. If there are at least 2 responders out of 11 in Arm B, accrual will continue to stage II until completion. Assuming an ORR of 10% in Arm A and 30% in Arm B, a sample size of 60 subjects will provide the necessary statistical precision for the observed differences between treatment arms. ClinicalTrials.gov identifier: NCT03795012.First patient enrolled on June 24th, 2019.

Citation Format: José Manuel Pérez-García, Alfonso Cortés Salgado, Elena López Miranda, Antonio Antón, Pedro Sánchez Rovira, Beatriz Castelo Fernández, Ana López González, Isabel Garau, Alejandro Martínez, Miguel Corbellas Aparicio, Sonia Del Barco, Miguel Sampayo, François Riva, Andrea Malfettone, Antonio Llombart-Cussac, Javier Cortés. A multicenter, randomized, phase II trial evaluating the efficacy of eribulin monotherapy and eribulin plus endocrine therapy in locally-recurrent or metastatic breast cancer patients after progression on endocrine therapy (REVERT study) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-09-01.