Abstract P1-12-05: 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 breast cancer
Authors: Cadoo K , Kaufman PA , Hudis C , Chang C , Berrak E , Song J , Seidman AD , Traina TA 
Published: May 2016

Abstract
Background: Eribulin has demonstrated antitumor activity and significantly improved overall survival (OS) in patients (pts) with heavily pretreated locally advanced/metastatic breast cancer (BC). This trial assessed the feasibility of eribulin as adjuvant therapy following dose-dense doxorubicin and cyclophosphamide (AC) for pts with human epidermal growth factor receptor 2 (HER2)-negative early-stage BC.
Methods: Pts with HER2(-), stage I–III, invasive BC were enrolled. Pts received dose-dense AC (doxorubicin 60 mg/m2 IV and cyclophosphamide 600 mg/m2 IV) on D1 of each 14-day cycle for 4 cycles with pegfilgrastim, followed by 4 cycles of eribulin (1.4 mg/m2 IV) on D1 and D8 every 21 days. Pts were divided into 2 cohorts: Cohort 1 did not receive any prophylactic growth factor (GF); Cohort 2 received a short course of prophylactic GF (filgrastim) on days 3, 4, 10, and 11 of each eribulin cycle. Primary endpoint of feasibility was determined as %pts who completed eribulin portion of the regimen without a dose delay (&gt;2 days) or reduction due to eribulin-related adverse event (AE). Based on similar previous studies, the target for feasibility was 80%. Relative dose intensity of eribulin and toxicities were also summarized by cohort. Exploratory objectives include efficacy endpoints of 3-yr disease-free survival and OS.
Results: We report data from 81 pts (55 Cohort 1; 26 Cohort 2) enrolled in the study, of whom 88% completed study treatment. Pt characteristics include median age 49 yrs (range 26–69), ECOG status 0 (85%), BC stages 1/2/3 (21%/57%/22%). Of 90% (73/81) pts evaluable for feasibility, 27% and 40% of pts in Cohorts 1 and 2, respectively, had dose delay or reduction during eribulin treatment, indicating the primary endpoint was not met. Overall, results were similar between the 2 cohorts (Table). Median duration of treatment with eribulin was 10.14 weeks in both cohorts (vs 10 weeks planned). Most eribulin-related dose delays were due to grade 3 (n=18) or grade 4 (n=7) neutropenia. Non-fatal serious AEs were observed in 11% of pts in Cohort 1 and 15% in Cohort 2. Discontinuations due to AEs occurred in 6% of pts in Cohort 1 and 0 in Cohort 2. Neutropenia (all grades) was reported in 36% of pts in Cohort 1 and 42% in Cohort 2. Most common AEs (all grades) were fatigue (96%), nausea (75%), alopecia (73%), hot flush (63%), and constipation (57%).
ACEribulin Cohort 1*Cohort 2*Cohort 1 (without GCSF)Cohort 2 (with GCSF)Relative dose intensity, mean99.5%99.0%92.0%90.9%Completed all planned doses98.2%96.2%87.0%84.0%Dose modification†12.7%15.4%35.2%40.0%GCSF, granulocyte-colony simulating factor. *With pegfilgrastim 6 mg given subcutaneously on D2 of each AC cyle; † including dose delays (&gt;2 days)/reduction/interruptions, missing, and permanent discontinuation due to AE.
Conclusions: The primary study endpoint of &gt;80% feasibility of planned dose delivery without any dose delays or reduction was not met. However, adjuvant treatment with dose-dense AC-eribulin was given safely, with two-thirds (67%) of pts achieving full dosing with no dose delay or reduction. Investigation into alternative dosing schedules or GF support is recommended.
Citation Format: Cadoo K, Kaufman PA, Hudis C, Chang C, Berrak E, Song J, Seidman AD, Traina TA. 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 breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-12-05.