Eribulin phase III trials
The efficacy and safety of eribulin in mBC treatment have been evaluated in two phase III trials, namely the EMBRACE study and Study 301 [2122].
The EMBRACE study was a global, multicenter, randomized (2:1) trial investigating eribulin versus a treatment of physician's choice (TPC) in 762 women with pretreated LABC or mBC. The primary endpoint of the study was OS. The TPC was used as the comparator arm to reflect the "real world" prescribing choices, since there is no standard therapy for mBC in the third-line setting. The women included in the study had received prior chemotherapy regimen, including anthracyclines and taxanes; either eribulin or TPC was subsequently administered as third- or later-line chemotherapy [21].
In the primary analysis with 422 events (55%), eribulin significantly extended the median OS compared with TPC (13.1 months vs. 10.6 months; hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.66–0.99; p=0.041). This represents a 23% increase in the 1-year median survival. An updated OS analysis including 589 events (77%), which was requested by the European and the United States regulatory authorities, confirmed a significant OS increase in eribulin-treated patients compared with those treated with the TPC (13.2 months vs. 10.5 months; HR, 0.81; 95% CI, 0.67–0.96; p=0.014) [21].
Based on an independent review, the median progression-free survival (PFS) was longer with eribulin treatment than with the TPC; however, this difference was not statistically significant (3.7 months vs. 2.2 months; HR, 0.87; 95% CI, 0.71–1.05; p=0.137) [21]. The objective response rate (ORR) was 12% (57 out of 468 patients) with eribulin treatment, including three cases with a complete response, versus 5% (10 out of 214 patients) with the TPC (p=0.002) [21].
In the other randomized phase III trial, Study 301, women with LABC or mBC who had received prior anthracycline- and taxane-based therapy (n=1,102) were randomized to receive either single agent eribulin or capecitabine as a first-, second-, or third-line chemotherapy. The co-primary end-points of the study were OS and PFS [22].
In Study 301, there was no statistically significant difference between eribulin and capecitabine with regard to the median OS (15.9 months vs. 14.5 months; HR, 0.88; 95% CI, 0.77–1.00; p=0.056) and the median PFS (4.1 months vs. 4.2 months; HR, 1.08; 95% CI, 0.93–1.25; p=0.30) [22]. Based on an independent review, the ORRs were 11% (95% CI, 8.5%–13.9%) and 11.5% (95% CI, 8.9%–14.5%; p=0.85) for eribulin and capecitabine, respectively [22].
A pooled analysis of the data from these two trials, as requested by the European Medicines Agency (EMA), was performed to assess whether specific patient subgroups benefited from eribulin treatment [23]. In this pooled analysis, eribulin improved the OS significantly in various patient subgroups, notably in patients with human epidermal growth factor receptor 2 (HER2)-negative and triple-negative (TN) disease. The results of this analysis were used as supplementary information to support the license extension of eribulin for second- and later-line therapy in mBC [23].
In addition to the overall analyses, a number of post-hoc analyses from the two phase III trials have been reported, and are presented in Table 3 [212425262728].