Abstract P3-13-05: Eribulin mesylate as first-line therapy for locally recurrent or metastatic HER2-negative breast cancer: Results of a phase 2, multicenter, single-arm study
Authors: McIntyre K , O'Shaughnessy J , Schwartzberg L , Glück S , Berrak E , Song J , Rege J , Cox D , Vahdat L 
Published: August 2014

Background: Eribulin mesylate is a novel nontaxane microtubule dynamics inhibitor that is approved for treatment of metastatic breast cancer (MBC) in patients who have previously received at least two chemotherapeutic regimens for MBC. We present final data from a phase 2 study that evaluated the efficacy and safety of eribulin as first-line therapy for HER2-negative (HER2-) MBC.

Methods: Patients with measureable HER2- locally recurrent or MBC with ≥12 months since prior neoadjuvant or adjuvant chemotherapy received eribulin mesylate 1.4 mg/m2 IV on days 1 and 8 of each 3-week cycle. Endpoints included objective response rate (ORR) (primary), safety, progression-free survival (PFS), time to response (TTR), and duration of response (DOR). Tumor assessments were conducted every 6 weeks for the first 6 cycles and every 6-12 weeks thereafter per RECIST 1.1.

Results: Fifty-six patients enrolled and received eribulin. Patients had a median age of 56 years (range 31-85); 32 (57%) had an ECOG status of 0; 17 (30%) had de novo stage IV; 33 (59%) had prior (neo)adjuvant therapy, including anthracycline and/or taxane (A/T) chemotherapy. Thirty-nine patients (70%) had visceral disease (45% liver, 32% lung); 41(73%) had estrogen receptor-positive (ER+) disease and 12 (21%) had triple negative (TN) disease. Thirty-two patients (57%) completed at least 6 cycles of treatment; among the 24 patients who completed fewer than 6 cycles, reasons for not completing were progressive disease (PD; n = 18), adverse events (AEs; n = 3) and patient choice (n = 3). The median number of cycles delivered was 7 (range 1-39); 6 patients (11%) received treatment for ≥12 months. Overall ORR was 27%, with median TTR of 1.4 months and median DOR of 7.4 months; stable disease (SD) rate was 48% (Table 1). Median PFS was 6.8 months. Thirty-five patients (63%) had grade 3/4 treatment-related AEs (Table 2). Treatment-related serious AEs occurred in 5 (9%) patients: neutropenia (5%), febrile neutropenia (5%), and leukopenia (2%).

Conclusions: The results of this study suggest that first-line eribulin has antitumor activity in ER+/HER2- and TN MBC with safety consistent with the known profile. Further exploration of this treatment as part of earlier lines of breast cancer therapy, including neo/adjuvant, is warranted.

Table 1. Summary of EfficacyEfficacyEribulin-treated patients N = 56ORR, n (%)15 (27)CR0PR15 (27)SD27 (48)PD12 (21)Clinical benefit rate (ORR + ≥6 mo SD)27 (48)Median months (95% CI) TTR1.4 (1.2, 2.7)DOR7.4 (4.7, NE)PFS6.8 (4.4, 7.4)NE, not estimable

Table 2. Treatment-Related AEsAE (N = 56)All events (%)Grade 3/4 (%)Leading to study drug withdrawal1111Leading to dose reduction3427Common AEs (≥25%)  Alopecia820Neutropenia7050Fatigue572Peripheral neuropathy5420Nausea460Anemia364Leukopenia3018Constipation270

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-13-05.