Efficacy of eribulin in women with metastatic breast cancer: a pooled analysis of two phase 3 studies

Abstract

Data from two phase 3 studies of eribulin were pooled in analyses initially requested by the European Medicines Agency to assess whether specific patient subgroups, previously treated with an anthracycline and a taxane, benefited from eribulin. Study 305/EMBRACE included women after two-to-five lines of chemotherapy for advanced breast cancer who were randomized to eribulin mesylate (1.4 mg/m2 on days 1 and 8 every 21 days) or treatment of physician’s choice. In Study 301, patients who had received up to two prior chemotherapy regimens for advanced disease were randomized to eribulin (as above) or capecitabine (1.25 g/m2 b.i.d. on days 1–14 every 21 days). In the pooled population, overall survival (OS), progression-free survival and response rates were analysed in the intent-to-treat population and selected subgroups. Overall, 1,062 patients were randomized to eribulin and 802 patients to control. Median OS was 15.2 months with eribulin versus 12.8 months with control (hazard ratio [HR] 0.85; 95 % CI 0.77, 0.95; P = 0.003). In all subgroups assessed, OS data favoured eribulin; significant improvements occurred in some subgroups, notably in women with human epidermal growth factor receptor 2 (HER2)-negative disease (HR 0.82; P = 0.002), although the effect in those with HER2-negative but hormone-receptor-positive disease did not reach statistical significance; benefits were also seen, among others, in those with estrogen-receptor-negative and triple-negative disease. Eribulin improves OS in various patient subgroups with advanced/metastatic breast cancer who had previously received an anthracycline and a taxane. Women with HER2-negative disease are among those who may obtain benefit from eribulin.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-014-3144-y) contains supplementary material, which is available to authorized users.

The histone deacetylase inhibitor OBP-801 and eribulin synergistically inhibit the growth of triple-negative breast cancer cells with the suppression of survivin, Bcl-xL, and the MAPK pathway

“…To identify a new strategy for the treatment of TNBC, we focused on eribulin, a well-tolerated chemotherapeutic agent against metastatic breast cancer that has promising efficacy, especially for TNBC [3]. Eribulin exerts its effects as a microtubule dynamic inhibitor via the different mechanism from other inhibitors such as taxanes and vinca alkaloids [18].…”

“…Since clinical data have indicated that eribulin is more effective for treating patients with TNBC than ER-positive breast cancer [3], we initially evaluated the inhibition of cell growth by eribulin in several human TNBC cell lines compared with ER-positive breast cancer MCF-7 cells. Eribulin inhibited the growth of the TNBC cell lines in a dose-dependent manner, and the result was more effective than that for MCF-7 cells ( Supplementary Fig.…”

“…A phase 3 randomized clinical trial (EMBRACE trial) showed that eribulin significantly improved the overall survival, and it has been approved for the treatment of refractory and metastatic breast cancer in Japan, the US, and Europe [2]. A subgroup analysis of this clinical trial also indicated that eribulin was more effective in patients with TNBC than estrogen receptor (ER)-positive breast cancer [3]. We administer eribulin as a monotherapy or in combination with anti-human epidermal growth factor receptor 2 (HER2) antibodies [4], and a clinical trial of eribulin and the anti-PD-1 antibody pembrolizumab therapy for metastatic TNBC is now in progress (ClinicalTrial.gov Identifier: NCT02513472).…”

Efficacy and Safety of Eribulin in Taxane-Refractory Patients in the “Real World”

“…It is worth of note that in this pooled study, a sub-group analysis showed that, compared to the control group, patients with triple negative subtypes obtained a slightly greater benefit in OS as compared to other patients subgroups, who achieved an OS benefit as well [30].…”

“…Median PFS was 3.7 mos in the first and 4.1 mos in the second phase III study. Twelves et al [30] pooled the results of these two randomized studies confirming a statistically significant OS benefit in favor of eribulin with a median OS of 15.2 mos as compared to 12.8 mos in the control arm.…”