(ChemotherapyAdvisor) – Eribulin mesylate demonstrated a trend favoring improved overall survival (OS) vs capecitabine in patients with locally advanced or metastatic breast cancer (MBC); however, the phase 3 study results did not meet coprimary endpoints for significance, according to results presented during the 2012 CTRC-AACR San Antonio Breast Cancer Symposium (SABCS).
“The study did not show a statistically significant benefit of eribulin over capecitabine, and it did not show a benefit in terms of progression-free survival (PFS), so the overall study objectives were not met,” said Peter A. Kaufman, MD, associate professor of medicine at the Geisel School of Medicine at Dartmouth and the Norris Cotton Cancer Center in Lebanon, NH.
“However, this is the first study demonstrating that eribulin is active in the first-, second- and third-line setting in metastatic breast cancer,” he added. Exploratory analyses suggest possible benefits of eribulin in specific subsets of patients, sufficient to warrant further study.
A total of 1,102 patients were randomly assigned to eribulin mesylate 1.4mg/m2 on days 1 and 8 of a 21-day cycle (n=554; 375 were HER2-negative) or oral capecitabine 2.5g/m2/day administered orally twice daily on days 1-14 of a 21-day cycle (n=548; 380 were HER2-negative). Prespecified statistical significance at final analysis for eribulin vs capecitabine were P≤0.0372 for OS and P<0.01 for PFS, the coprimary endpoints.
Median age was 54.0 years (range, 24-80 years). Patients received study treatment as their first-line (27.2%), second-line (57.4%), or third-line (14.7%) chemotherapeutic regimen in the setting of metastatic disease. Median number of treatment cycles was 6 for eribulin and 5 for capecitabine.
Median OS was 15.9 months for eribulin vs 14.5 months for capecitabine (HR 0.879; 95% CI 0.770–1.003; P=0.056), and PFS by independent review was 4.1 and 4.2 months (HR 1.079; 95% CI 0.932–1.250; P=0.305), respectively.
Objective response rate by independent review was 11.0% (95% CI 8.5–13.9) for eribulin and 11.5% (95% CI 8.9–14.5; P=0.849) for capecitabine.
Exploratory analyses of patient subsets showed median OS in women with HER2-negative breast cancer was 15.9 months with eribulin vs 13.5 months with capecitabine (HR 0.838; 95% CI 0.715–0.983; P=0.030). In women with triple-negative breast cancer, median OS was 14.4 months with eribulin vs 9.4 months with capecitabine.
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.
In 2010, the FDA approved eribulin for the treatment of patients with MBC who had previously received an anthracycline and a taxane and at least two cytotoxic chemotherapy treatment regimens for MBC. The FDA granted approval based on data showing a statistically significant improvement in OS vs current treatments.