Abstract OT1-01-01: A phase II, open-label, multicenter, translational study for biomarkers of eribulin mesylate: Evaluation of the utility of monitoring epithelial-to-mesenchymal transition (EMT) markers on tumor cells in the malignant plural effusion of patients with metastatic breast cancer (EXPECT-study)
Authors: Watanabe J , Ohtani S , Ikeda M , Takahashi M , Moriya T 
Published: March 2017

Abstract
Background: Epithelial-mesenchymal transition (EMT) is considered a possible mechanism of distant metastasis or resistance of cancer cells to anticancer drugs. Several reports suggest that eribulin methylate (eribulin) promotes mesenchymal-epithelial transition (MET) both in vitro and in vivo and have shown its inhibition of distant metastasis of engrafted carcinoma. However, no reports have examined the effects of eribulin in a clinical setting. The EXPECT-study investigates EMT/MET markers in metastatic breast cancer (MBC) patients using pleural effusion as a method of liquid biopsy.
Objectives: In MBC patients with malignant pleural effusion, we attempted to establish EMT/MET markers using the cancer cells in the pleural effusion, to assess the efficacy and safety of eribulin monotherapy, and to verify the EMT/MET markers as biomarkers in eribulin monotherapy.
Study design and eligibility criteria: The EXPECT study is a multicenter, open-label, single-arm phase 2 translational study. Eribulin will be administered at 1.4 mg/m2 on Days (D) 1 and 8 for a 3-week cycle (C), and to obtain the cancer cells from the pleural effusion before and after eribulin administration, paired chest drainage will be performed on C1D1 and C1D8. MBC patients, regardless of their subtype, with pleural effusion are eligible for enrollment, and eribulin monotherapy in the study will be administered based on clinical practice. Therefore, there are no special inclusion/exclusion criteria except for the requirement that all patients be naïve to eribulin.
Methods: Spun-down cancer cells in the plural effusion will be processed via the cell block method and embedded in paraffin. An immunohistochemical analysis will be performed using candidate antibodies for EMT/MET markers, such as E-cadherin, cytokeratin (CK) 19, and 34betaE12 (CK1, CK5, CK10, CK14) as epithelial markers and N-cadherin, vimentin, Snail, Slug, Twist-1, ZEB1, ZEB2, ALDH1, and HIF-1alpha as mesenchymal markers, which are all concurrently being assessed in another confirmatory study. The changes in EMT/MET marker expression between pre- and post-treatment will be measured, and the relationship between these changes and the clinical outcome, such as the clinical benefit rate (CBR), progression-free survival, and overall survival, will be assessed.
Present and target accrual: The study was just approved by the institutional review board in March 2016 and is open for enrollment. The target accrual is 48 patients total, or 4 patients per month. The sample size calculation was not based on statistical consideration, such as power or type I error. As an illustration for the analysis, the relationship between the changes in the EMT/MET markers and the clinical outcome may be investigated by comparing the CBRs in the two groups with substantial and small changes in the marker expression. If we demonstrate CBRs of 38% and 13% in each group, respectively, then statistical significance will be demonstrated with a 0.10 significance level (2-sided).
Citation Format: Watanabe J, Ohtani S, Ikeda M, Takahashi M, Moriya T. A phase II, open-label, multicenter, translational study for biomarkers of eribulin mesylate: Evaluation of the utility of monitoring epithelial-to-mesenchymal transition (EMT) markers on tumor cells in the malignant plural effusion of patients with metastatic breast cancer (EXPECT-study) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-01-01.