Abstract OT2-2-05: Metronomic eribulin in metastatic breast cancer
Authors: Chalasani Pavani , Robert Livingston B , Rado Thomas A , Gadi Vijayakrishna K , Kummet Thomas D , Specht Jennifer M , Stopeck Alison , Linden Hannah M 
Published: May 2015

Abstract
Introduction: Breast cancer is a common and curable malignancy. In the setting of late or early recurrence, improvement in therapy is indicated as overall survival (OS) has changed little over the past few decades. Eribulin mesylate is a non-taxane microtubule dynamics inhibitor FDA approved in salvage metastatic breast cancer (MBC) treatment based on improvements in OS. Eribulin mesylate is a synthetic analogue of halichondrin B, a product isolated from the marine sponge Halichondria okadai.
Anti-tubulin therapy is an established cornerstone of chemotherapeutics for MBC. Work at our center and others has shown a favorable therapeutic index for weekly metronomic vinorelbine. The history of other effective and tolerable agents, including paclitaxel, capecitabine, and vinorelbine, suggests that a low dose metronomic schedule of eribulin could be effective, well tolerated and result in longer time to progression (TTP), and higher quality of life during therapy. In phase I studies, Eribulin showed activity at doses well below the maximally tolerated 1.4mg/m2 given 2/3 weeks, suggesting a lower metronomic schedule would not compromise efficacy. A lower dose metronomic schedule will allow responding patients to remain on treatment, resulting in longer TTP and greater use of the drug in practice.
Study Design: This is an open-label, multi-center, phase II study of eribulin for patients with MBC. HER2 positive patients may enroll with concomitant use of trastuzumab. Patients will receive eribulin 0.9 mg/m2 administered intravenously over 2 to 5 minutes on Days 1¸ 8 and 15 of a 28-day cycle. Treatment will be continued until disease progression, unacceptable toxicity or withdrawal of patient consent.
Eligibility Criteria: Patients with MBC whose disease has progressed following 1-6 prior regimens with prior exposure to a taxane, ECOG PS of 0 – 2, measurable disease per RECIST 1.1, normal marrow and organ function.
Patients with known CNS metastases must have stable disease off steroids after treatment with surgery or radiation. Exclusion criteria: mild hepatic or renal impairment, grade &gt; 2 peripheral neuropathy, significant cardiovascular impairment or other severe or uncontrolled medical disease or psychiatric or neurologic disorder.
Specific Aims: The primary aim is to increase progression free survival (PFS). We hypothesize that metronomic dosing of eribulin will result in PFS of 4-6 months.
Secondary aims include decreasing the frequency of alopecia to less than 50%, grade 3 or 4 neutropenia to less than 30% and sensory neuropathy (all grades) to less than 25% of subjects enrolled.
An exploratory aim is to assess the role of circulating endothelial cell precursors (CEPs) and apoptotic circulating endothelial cells in predicting early response to treatment.
Statistical Methods: PFS will be measured as the time from study enrollment until the earliest date of disease progression or death. The sample size of n=60 has 99% power for the lower bound of the confidence interval to be greater than 2.2 months (the median PFS in the physician’s discretion arm of the EMBRACE trial), assuming that the true median PFS is 4 months, comparable to or an incremental improvement over the median PFS for the eribulin arm of the EMBRACE trial (3.7 months).
Currently 12 of 60 expected enrollments have occurred.
Citation Format: Pavani Chalasani, Livingston B Robert, Thomas A Rado, Vijayakrishna K Gadi, Thomas D Kummet, Jennifer M Specht, Alison Stopeck, Hannah M Linden. Metronomic eribulin in 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 OT2-2-05.