Background: Metastatic breast cancer (MBC) is an incurable disease and is needed to improve effective chemotherapy. Paclitaxel plus Gemcitabine (PG) combination chemotherapy is one of the preferred chemotherapeutic regimens for patients with MBC, and was found to be proper as a maintenance chemotherapy regimen with survival benefit and feasible toxicity profile. Eribulin mesylate is a non-taxane inhibitor of microtubule dynamics of the halichondrin class of antineoplastic drugs. A recent pooled analysis of two phase II studies with eribulin showed improved overall survival in in various patient subgroups with advanced/metastatic breast cancer who had previously received an anthracycline and a taxane. Furthermore, eribulin may have rational benefit compared with paclitaxel in terms of neurotoxicity. Therefore, Eribulin plus Gemcitabine (EG) combination chemotherapy may have less neurotoxocity comparing to PG.

Trial Design: Prospective randomized phase 2, open-label, two-arm, multi-center study comparing EG chemotherapy with PG chemotherapy for patients with HER-2 negative MBC as first-line chemotherapy.

Eligibility Criteria: Histologically confirmed breast cancer patients, at least 19 years of age, with no prior history of chemotherapy for metastatic, recurrent breast cancer with evaluable lesions (as per RECIST, 1.1) who have adequate hematologic, renal, and hepatic function. Patients either may or may not have a prior anthracycline containing regimen. Prior hormonal therapy as a treatment of metastatic disease is allowed.

Specific Aims:

The primary efficacy endpoint of the trial is Progression-Free Survival (PFS). The secondary efficacy endpoints are: Time to Treatment Failure (TTF); Overall Survival (OS); neuropathic scale (FACT for Taxane QOL assessment); toxicity; duration of response; Objective Response Rate (ORR); Clinical Benefit Rate. The exploratory endpoint of the study includes pharmacogenetic profile.

Statistical Methods:

The initial sample size of the present study was determined based on the data derived from a previous trial on PG maintenance chemotherapy design; 6-month PFS is 70% for PG chemotherapy. This design was hypothesized that EG chemotherapy would not be inferior to PG chemotherapy. Thus, estimated PFS for each arm is 70%. Based on this estimate, we would plan to recruit a total of 100 patients (50 per arm). Considering drop-out rate of 10%, total 112 MBC patients planned to be enrolled.

Present Accrual and Target Accrual:Enrollment has been completed as of March, 2016 with a target enrollment of 112 patients.

Contact information:Kyung Hae Jung MD, Ph.D. Identifier: NCT02263495.

Citation Format: Park YH, Im S-A, Sohn JH, Lee KS, Chae YS, Lee KH, Kim J-H, Im Y-H, Ahn JS, Kim T-Y, Lee K-H, Kim S-B, Ahn J-H, Kim GM, Park IH, Lee SJ, Han HS, Kim SH, Jung KH. A phase II, multicenter, randomized trial of eribulin plus gemcitabine (EG) vs. paclitaxel plus gemcitabine (PG) in patients with HER2-negative metastatic breast cancer as first-line chemotherapy [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 OT1-01-12.