Abstract P1-13-11: Adjuvant treatment of early-stage breast cancer with eribulin mesylate following dose-dense doxorubicin and cyclophosphamide: preliminary results from a phase 2, single-arm feasibility study
Authors: Traina TA , Hudis C , Fornier M , Lake D , Lehman R , Berkowitz AP , Rege J , Liao J , Cox D , Seidman AD 
Published: August 2014

Abstract
Background: Despite recent improvements in breast cancer outcomes, patients (pts) with high-risk, early-stage breast cancer continue to experience recurrences and death due to disease. Chemotherapy regimens with the ability to extend survival remain an important drug development goal. Eribulin mesylate has demonstrated antitumor activity and improved overall survival (OS) in pts with heavily pretreated, locally recurrent or metastatic breast cancer when compared to treatment of physician's choice. This study examines the feasibility of eribulin as adjuvant therapy following dose-dense (dd) doxorubicin (A) and cyclophosphamide (C) in patients with early-stage breast cancer.
Methods: Eligible pts have histologically confirmed, HER2-normal, stage I-III invasive breast cancer and adequate bone marrow, liver, and renal function. Treatment consists of dd AC (A 60mg/m2 IV; C 600mg/m2 IV) on Day 1 of each 14-day cycle x4 cycles, followed by eribulin mesylate 1.4mg/m2 IV over 2–5min on Days 1 and 8 every 21 days x4 cycles. Radiation/hormonal therapy were allowed per standard of care. The primary objective of feasibility is defined as the ability to complete 4 cycles of eribulin without a treatment-related dose delay (defined as &gt;2 days) or reduction. Feasibility rates will be reported for pts with and without growth factor use. Secondary/exploratory endpoints include evaluation of the safety via NCI-CTCAEv4 of 4 cycles of AC followed by 4 cycles of eribulin, and 3-year disease-free survival and OS.
Results: As of 5/22/12, 46 of 80 planned pts have been treated; 38 pts have had ≥1 dose of eribulin and are evaluable for eribulin-related toxicity. Pt characteristics are as follows: median age 50 yrs (27–65 yrs); 100% female; ECOG of 0=81.6%; breast cancer stage at study entry: stg 1: 7.5%; stg 2: 72.5%, stg 3: 20%. Select treatment-related AEs are reported as total (all cycles) and eribulin-related events; many AEs overlapped during treatment (Table).

Serious treatment-related AEs were reported in 2 pts, the most common (5.3%) being febrile neutropenia attributed to AC. Currently, 13 pts have had eribulin dose modification or delays; 10 of the events were related to eribulin (7 reductions, 5 delays, 1 withdraw). Eribulin-related AEs associated with dose delay or reduction are: 6 gr-3 neutropenia, 1 gr-3 febrile neutropenia, 1 gr-3 peripheral neuropathy, 1 gr-3 respiratory infection, 1 gr-3 fatigue. Six pts have discontinued (DC) treatment (2 AEs, 1 disease recurrence, 3 withdrew consent). Five of the 6 pts requiring eribulin delay/modification due to neutropenia were able to complete therapy with growth factor support. One pt DC eribulin therapy due to neuropathy.
Conclusions: Preliminary results from this study suggest that adjuvant treatment with eribulin following dose-dense AC therapy has an acceptable safety profile. Accrual is ongoing and study completion is anticipated prior to SABCS 2012.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-11.