A phase II, single-arm, feasibility study of dose-dense doxorubicin and cyclophosphamide (AC) followed by eribulin mesylate for the adjuvant treatment of early-stage breast cancer (EBC).

Abstract

TPS1145 Background: Randomized trials have confirmed the benefit of the combination of an anthracycline (A) and cyclophosphamide (C) for the adjuvant treatment of EBC. The addition of taxane therapy to AC therapy has further improved survival. Despite the improvement in adjuvant therapies for BC, new approaches for improving outcomes are of significant importance and may involve developing improved combination regimens. Eribulin mesylate has demonstrated antitumor activity and significant improvement in overall survival (OS) in patients with heavily pretreated locally advanced or metastatic breast cancer (MBC) and may improve outcomes in EBC as well. Methods: This study will determine the feasibility of eribulin as adjuvant therapy following dose-dense AC for HER2 normal EBC. A completion rate of >80% was set as a threshold for feasibility as established adjuvant regimens have shown feasibility rates ranging from ~65% for trastuzumab to >80%. This is a phase 2, single-center, feasibility study of dose-dense adjuvant chemotherapy in patients with EBC. Dose-dense AC (Doxorubicin 60 mg/m2 IV plus C 600 mg/m2 IV) on day 1 of every 14-day cycle is given for 4 cycles, followed by 4 cycles of eribulin mesylate at 1.4 mg/m2 over 2-5 minutes IV on days 1 and 8 every 21 days. Growth factors are given on day 2 of AC cycles and only for neutropenia events with eribulin treatment. Feasibility is determined by the ability to complete the eribulin portion of the regimen without a dose delay or reduction. Exploratory objectives include efficacy endpoints of 3-year disease-free survival (DFS) and OS. Patients have histologically confirmed HER2 normal stage I-III invasive disease and adequate bone marrow, liver, and renal function. Thirty two of approximately 80 planned patients are currently enrolled. Feasibility rates will be calculated with growth factor support (ie, the successful use of growth factor support following a neutropenia event is not considered a dose delay)and without growth factor support (ie, where need for growth factors is considered a delay). Secondary endpoints include DFS and OS and will be estimated by Kaplan-Meier method.