[T]his trial did not demonstrate superiority of eribulin versus capecitabine for either [overall survival] or [progression-free survival].
—Peter A. Kaufman, MD, and colleagues
Eribulin (Halaven) currently is indicated in the United States for treatment of patients with metastatic breast cancer who previously received at least two chemotherapy regimens for metastatic disease and an anthracycline and a taxane in either the adjuvant or metastatic setting. Its approval was based on a phase III trial showing a survival advantage for eribulin vs single-agent treatment of the physician’s choice.1 In a phase III trial reported in the Journal of Clinical Oncology, Peter A. Kaufman, MD, of Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, and colleagues found no overall survival advantage for eribulin vs capecitabine.2
In this open-label trial, 1,102 women with locally advanced or metastatic breast cancer who had received up to three chemotherapy regimens and up to two prior chemotherapy regimens for advanced and/or metastatic disease with an anthracycline and a taxane were randomly assigned to receive eribulin at 1.4 mg/m2 IV on days 1 and 8 (n = 554) or oral capecitabine at 1.25 g/m2 twice daily on days 1 to 14 (n = 548) every 21 days. The primary endpoints were overall survival and progression-free survival.
The eribulin and capecitabine groups were generally balanced for all characteristics considered. Overall, 20%, 52%, and 27% received study therapy as first-line, second-line, and third-line treatments for advanced disease.
Median overall survival was 15.9 months (95% confidence interval [CI] = 15.2–17.6 months) in the eribulin group vs 14.5 months (95% CI = 13.1–16.0 months) in the capecitabine group (hazard ratio [HR] = 0.88, 95% CI = 0.77–1.00, P = .056). Median progression-free survival was 4.1 months (95% CI = 3.5–4.3 months) vs 4.2 months (95% CI = 3.9–4.8 months; HR = 1.08, 95% CI = 0.93–1.25, P = .30). Objective response rate on independent review was 11.0% vs 11.5% (P = .85). A prespecified exploratory analysis suggested an overall survival benefit for eribulin in HER2-negative patients; however, there was no significant interaction between treatment effect and HER2 status.
The most common adverse events of any grade were neutropenia (54%), alopecia (35%), leukopenia (31%), global peripheral neuropathy (27%), and nausea (22%) in the eribulin group and hand-foot syndrome (45%), diarrhea (29%), and nausea (24%) in the capecitabine group. The most common grade 3 or 4 adverse events were neutropenia (46%), leukopenia (15%), and global peripheral neuropathy (7%) in the eribulin group, and hand-foot syndrome (15%) in the capecitabine group. Febrile neutropenia occurred in 2.0% vs 0.9%. Colony-stimulating factor treatment was required in 15% vs 4%.
Adverse events led to discontinuation, reduction, and delay in treatment in 8% vs 10%, 32% vs 32%, and 32% vs 36%. The most common causes of treatment discontinuation were neutropenia (1.7%) in the eribulin group and hand-foot syndrome (2.2%) and dyspnea (1.1%) in the capecitabine group.
Serious adverse events occurred in 18% of the eribulin group vs 21% of the capecitabine group. Fatal adverse events occurred within 30 days of the last study dose in 4.8% of eribulin recipients and 6.6% of capecitabine recipients; these events were considered treatment-related in five eribulin patients (sepsis, pericardial effusion, sudden death, toxic hepatitis, and renal failure) and four capecitabine patients (sepsis, pneumonia, cardiogenic shock, and pancytopenia).
Global health status/overall quality of life was assessed by the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire C30 (version 3.0) and breast module Quality-of-Life Questionnaire BR23. Both groups had improvement in average scores during the study, with no between-group differences being observed.
The investigators concluded: “[T] his trial did not demonstrate superiority of eribulin versus capecitabine for either [overall survival] or [progression-free survival]. The effects on [quality of life] in this population of patients with [metastatic breast cancer] and the [adverse event] profiles of eribulin and capecitabine were consistent with their known [adverse events].” ■
Disclosure: This study was supported by Eisai. For full disclosures of the study authors, visit www.jco.org.
1. Cortes J, O’Shaughnessy J, Loesch D, et al: Eribulin monotherapy versus treatment of physician’s choice in patients with metastatic breast cancer (EMBRACE): A phase 3 open-label randomised study. Lancet 377:914-923, 2011.
2. Kaufman PA, Awada A, Twelves C, et al: Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 33:594-601.