Abstract S6-6: A Phase III, open-label, randomized, multicenter study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxanes

Abstract

Background: Eribulin is a non-taxane microtubule dynamics inhibitor. In a previous Phase III trial, eribulin demonstrated a statistically significant improvement in overall survival (OS) versus current treatments and a manageable toxicity profile, in heavily pre-treated patients (pts) with metastatic breast cancer (MBC). Here we report results from a Phase III trial of eribulin compared with capecitabine in earlier-line pts with MBC (NCT00337103). Patients and methods: Pts were randomized 1:1 to eribulin mesylate 1.4 mg/m2 given on Days 1 and 8 of a 21 day cycle or capecitabine 2.5 g/m2/day administered orally BID on Days 1 to 14 of a 21 day cycle. Eligible pts had received prior therapy including an anthracycline and taxane, and were receiving study drug as 1st, 2nd, or 3rd line therapy for advanced disease. The co-primary endpoints of this study were OS and progression free survival (PFS): pre-specified statistical significance at final analysis for eribulin versus capecitabine were p ≤ 0.0372 for OS and p < 0.01 for PFS. Secondary endpoints included objective response rate (ORR), quality of life (QoL) measured using the EORTC questionnaire, duration of response, 1-, 2- and 3-year survival, and safety. The study was stratified for geographic region and HER2 status. Results: Of 1102 pts, 554 were randomized to eribulin and 548 capecitabine (375 and 380 pts were HER2[−], respectively). The median age was 54.0 years (range 24–80). Pts received study treatment as their 1st (27.2%), 2nd (57.4%) or 3rd-line (14.7%) chemotherapeutic regimen in the setting of metastatic disease. The median number of treatment cycles was 6 for eribulin and 5 for capecitabine. Median OS was 15.9 and 14.5 months (hazard ratio [HR] 0.879; 95% confidence intervals [CI] 0.770–1.003; p = 0.056), and PFS (independent review) was 4.1 and 4.2 months (HR 1.079; 95% CI 0.932–1.250; p = 0.305) for eribulin and capecitabine, respectively. ORR (independent review) were 11.0% (95% CI 8.5–13.9) and 11.5% (95% CI 8.9–14.5; p = 0.849), respectively. OS for HER2(−) pts was 15.9 months for eribulin and 13.5 months for capecitabine (HR 0.838; 95% CI 0.715–0.983; p = 0.030). AEs were consistent with the known side-effect profiles of both drugs. The most common AEs for eribulin and capecitabine (>20% all grades) were neutropenia (54.2% vs 15.9%), hand-foot syndrome (0.2% vs 45.1%) alopecia (34.6% vs 4.0%), leukopenia (31.4% vs 10.4%), diarrhea (14.3% vs 28.8%), and nausea (22.2% vs 24.4%), respectively. Conclusion: In this Phase III trial, eribulin demonstrated a trend favoring improved OS, compared with capecitabine, although this improvement does not meet the pre-defined criteria for statistical significance. This study confirms eribulin as an active drug in pts with MBC, and exploratory analyses suggest possible benefits of eribulin in specific subsets of pts, sufficient to warrant further study. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr S6-6.

ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2)

“…Eribulin has provided an OS benefit in heavily pretreated patients (up to 5 lines of treatment) [115] and similar PFS and OS results to capecitabine after prior treatment with an anthracycline and taxane [116].…”

Phase II neoadjuvant clinical trial of carboplatin and eribulin in women with triple negative early-stage breast cancer (NCT01372579)

“…Most toxicities were grade 1 and 2, and the most common reason for dose [28,29] and platinum agents [26,30] in TNBC. DNA double-strand break repair by homologous recombination (HR) is required for the repair of DNA damage arising from many currently used DNA-damaging chemotherapy agents [31].…”

Treating Triple-Negative Breast Cancer: Where Are We?

“…30 The phase III "301" trial compared eribulin with capecitabine in 1102 pretreated patients with MBC, and reported a significant improvement in median OS associated with eribulin among the subset of patients with TNBC in an exploratory analysis (14.4 vs 9.4 mo; HR, 0.7; P=.01). 31 However, in the published version of this study, the authors did not report any significant difference in benefit among the subgroups.…”