Abstract P6-12-15: Efficacy results of a phase 1/2 study of glucocorticoid receptor (GR) antagonist mifepristone (MIFE) in combination with eribulin in GR-positive triple-negative breast cancer (TNBC)
Authors: Han HS , Wilks S , Paplomata E , Modiano MR , Becerra C , Braiteh FS , Spira AI , Pluard TJ , Richards DA , Conzen SD , Baker G , Fishman RS , Marcantonio A , O'Shaughnessy J , Nanda R 
Published: March 2017

Abstract
Background: GR is variably expressed in TNBC and high expression is associated with poor prognosis in estrogen receptor-negative (ER-) early stage breast cancer. Treatment with mifepristone (MIFE) potentiates the effectiveness of chemotherapy in GR+ TNBC xenografts. Enrollment is complete in this study of patients with GR+ TNBC treated at the recommended Phase 2 dose (RP2D) of MIFE in combination with eribulin. Objectives: To determine the safety, tolerability, pharmacokinetics (PK) and clinical activity of the MIFE plus eribulin combination in pts with GR+ TNBC at the RP2D. Methods: Eligibility: In Part 1 (dose finding), pts with solid tumors; in Part 2 (expansion phase), pts with TNBC (GR result required at time of screening in Part 1, but could be pending at time of screening in Part 2). Up to 5 prior chemotherapy regimens for advanced disease; ECOG PS 0-1; adequate end-organ function. Design: 3 + 3 dose escalation scheme. After a 7-day lead-in of oral daily MIFE alone, MIFE was continued daily and eribulin was given on days 1 and 8 of a 21-day cycle. GR+ was defined as &gt;10% of tumor cells with any intensity of GR staining. Results: 16 pts with metastatic breast cancer were treated in Part 1, and 21 pts with TNBC were treated in Part 2. Median age was 54 (range 30-81). MTD/RP2D was MIFE 300 mg/day + eribulin 1.1 mg/m2. Safety: DLT in Part 1 was neutropenia. Neutropenia occurred in 23/36 total patients (2 Grade [G] 1, 10 G3, 11 G4); 2 instances included neutropenic fever. Recovery of WBC was brisk with growth factor support. Neuropathy was observed in 8 pts (5 G1, 1 G2, 2 G3). Other most common AEs (fatigue, hypokalemia, nausea, alopecia) were mainly G1 or G2; among these, G3/G4 events were limited to fatigue (4 G3), hypokalemia (3 G3 and 1 G4) and nausea (1 G3). There were 2 instances of G1 vaginal bleeding. There was no impact of MIFE on eribulin PK. Efficacy: There were 23 evaluable pts with TNBC across Parts 1 and 2 treated at the RP2D: 21 GR+, 2 GR status unknown; median of 3 prior chemotherapy regimens; 1 patient had received prior eribulin. Responses were: 3 PR, 8 SD, 11 PD and one too early to assess. Median PFS was 9 weeks. Conclusions: MIFE plus eribulin was well tolerated and appears to be an active treatment regimen. Five TNBC patients had a PFS longer than the upper 95% CI for PFS (i.e., &gt;15 wks) reported by Aogi et al. for TNBC treated with eribulin (Annals of Oncology 2012?23:144148). Clinical trial information: NCT02014337.
Citation Format: Han HS, Wilks S, Paplomata E, Modiano MR, Becerra C, Braiteh FS, Spira AI, Pluard TJ, Richards DA, Conzen SD, Baker G, Fishman RS, Marcantonio A, O'Shaughnessy J, Nanda R. Efficacy results of a phase 1/2 study of glucocorticoid receptor (GR) antagonist mifepristone (MIFE) in combination with eribulin in GR-positive triple-negative breast cancer (TNBC) [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 P6-12-15.