Phase 2 Study of Dose-Dense Doxorubicin and Cyclophosphamide Followed by Eribulin Mesylate With or Without Prophylactic Growth Factor for Adjuvant Treatment of Early-Stage Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.

BACKGROUND: Eribulin has significantly improved overall survival for patients with metastatic breast cancer who received ≥ 2 prior chemotherapy regimens for advanced disease. This trial assessed eribulin as adjuvant therapy for patients with early-stage breast cancer. PATIENTS AND METHODS: Patients with human epidermal growth factor receptor 2-negative, stage I to III breast cancer received doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 provided intravenously on day 1 of each 14-day cycle for 4 cycles, with pegfilgrastim on day 2, followed by 4 cycles of eribulin mesylate 1.4 mg/m2 provided intravenously on days 1 and 8 every 21 days. There were 2 cohorts, as follows: cohort 1: no prophylactic growth factor with eribulin (allowed at physician's discretion only); cohort 2: prophylactic filgrastim with eribulin. The primary end point was feasibility, defined as the percentage of patients who completed the eribulin portion of the regimen without a dose omission, delay, or reduction due to an eribulin-related adverse event. Relative dose intensity of eribulin and toxicities are summarized by cohort. Exploratory end points included 3-year disease-free survival and overall survival.
RESULTS: Eighty-one patients (cohort 1, n = 55; cohort 2, n = 26) entered the treatment phase; 88% completed treatment. Feasibility was 72.9 % (90% confidence interval, 60.4, 83.2) in cohort 1 and 60.0% (90% confidence interval, 41.7, 76.4) in cohort 2. The most frequent eribulin-related adverse events (all grades) were fatigue (75.9%), peripheral neuropathy (54.4%), nausea (39.2%), neutropenia (35.4% [31.5% of patients in cohort 1; 44.0% in cohort 2]), and arthralgia (26.6%).
CONCLUSION: The primary end point of > 80% feasibility was not met. No unexpected adverse events were observed, and 62% of patients received full dosing with no dose delay or reduction. Further investigation of this regimen with alternative dosing schedules or use of growth factors could be considered.