Eribulin Plus Gemcitabine (EG) vs Paclitaxel Plus Gemcitabine (PG) in HER2-Negative Metastatic Breast Cancer

Summary

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 as shown in a large phase III KCSG (Korean Cancer Study Group) study (Park Y et al. J Clin Oncol 31(14):1732, 2013). Eribulin mesylate is a microtubule-targeting agent that showed improved overall survival benefit as monotherapy for MBC patients as a new chemotherapeutic agent after failure of anthracycline and taxane in EMBRACE study (Cortes J et. al. Lancet 377:914-923, 2011). Eribulin was also reported its promising efficacy in another randomized phase III study that demonstrated eribulin as efficacious as capecitabine (Kaufman P et. al. Abstr# S6-6, SABCS 2012). Both study results showed potential clinical benefit in patients with triple negative MBC (TNBC). Thus, eribulin combined with gemcitabine may be a new potential regimen for early line therapy in patients with metastatic breast cancer. Furthermore, eribulin may have rational benefit compared with paclitaxel in terms of neurotoxicity. Although there is no direct evidence that eribulin has better neurotoxicity profile than taxane, eribulin tended to show less neurotoxicity compared with ixabepilone in a phase II trial (Vahdat, L et al. 2011 SABCS). Eribulin has no worsen toxicity as compared to paclitaxel. Therefore, EG may have less neurotoxicity comparing to PG. In phase I trial, eribulin in combination with gemcitabine was feasible in patients with advanced solid tumor treated with chemotherapy (\< 3 lines) (Goel R, et al, 2009 ASCO). Based on this rationale, the investigators are to conduct randomized phase II study comparing EG chemotherapy with PG chemotherapy for patients with HER-2 negative MBC as first-line chemotherapy. A total of 118 patients will be recruited. Patients will be randomized to a treatment arm by permutated method. The randomization ratio is 1:1. This study is multi-center, randomized, open label study.

Timeline

Start

2014-12-19

Primary completion

2017-05-11

Completion

2019-06-17

Publications

• Kim JY, Lee E, Park K, Im SA, Sohn J, Lee KS, Chae YS, Kim JH, Kim TY, Jung KH, Park YH; Breast Cancer Committee of the Korean Cancer Study Group. Exploratory biomarker analysis from a phase II clinical trial of eribulin plus gemcitabine versus paclitaxel plus gemcitabine for HER2-negative metastatic breast cancer patients (KCSG BR13-11). Breast Cancer Res Treat. 2019 Nov;178(2):367-377. doi: 10.1007/s10549-019-05400-y. Epub 2019 Aug 12.
• Park YH, Im SA, Kim SB, Sohn JH, Lee KS, Chae YS, Lee KH, Kim JH, Im YH, Kim JY, Kim TY, Lee KH, Ahn JH, Kim GM, Park IH, Lee SJ, Han HS, Kim SH, Jung KH; Korean Cancer Study Group (KCSG). Phase II, multicentre, randomised trial of eribulin plus gemcitabine versus paclitaxel plus gemcitabine as first-line chemotherapy in patients with HER2-negative metastatic breast cancer. Eur J Cancer. 2017 Nov;86:385-393. doi: 10.1016/j.ejca.2017.10.002. Epub 2017 Nov 5.

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