MERIBEL study: Single-agent eribulin as first-line therapy for taxane-resistant HER2[-] metastatic breast cancer (MBC) patients (pts)

Abstract

Background: Eribulin improved overall survival (OS) in ≥3 line treatment of MBC pts. In a large retrospective study, short disease-free interval (DFI) and prior taxane therapy have been associated with worse OS in pts receiving first-line chemotherapy for HER2[-] MBC. The aim of MERIBEL trial is to evaluate the efficacy and safety of eribulin as first-line therapy for HER2[-] MBC pts with these poor prognostic factors. Methods: Phase II, multicenter, single arm, trial. Eribulin (1.23 mg/m2) as single-agent was administered on days 1 and 8 of 21 day cycles until progression or unacceptable toxicity. Principal selection criteria: (1) HER2[-] pts without prior chemotherapy for MBC; (2) prior taxane therapy (≥4 cycles) for early BC; (3) less than 36 months* (mo) between the last taxane cycle and relapse; (4) RECIST v1.1 evaluable disease; (5) no symptomatic brain involvement. (*) Amendment to 48 mo. Primary outcome was time to progression (TTP). Secondary endpoints included OS, progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR) and toxicity. We included 53 women from 61 pts recruited between SEP/2013 to MAR/2015 across 12 sites and 2 countries. Results: Median age 51 years [range 23-83]; 50.9% were ECOG 0; 45.3% were triple-negative; 84.9% received prior anthracyclines. Median DFI was 15.7 mo [0.1-46.5]; and 52.8% had visceral metastases (11.3% with ≥3 involved organ sites). Median follow-up was 12.7 mo [0.2 – 30.5]. Median TTP was 4.1 mo [95%CI 2.2-6], median PFS was 4.3 mo [2.2-6.5], and median OS has not been reached yet. The 1-year TTP, PFS and OS rates were 16.2%, 24.3%, and 65.9%, respectively. The ORR was 20.8% and CBR, 26.4%. Eribulin all grades and 3/4 adverse events (AEs) were reported in 96.2% and 71.7% of the pts, respectively. The most common grade 3/4 AEs were neutropenia (28.3%), leukopenia (17%), peripheral neuropathy (5.7%) and asthenia (5.7%). One patient experienced febrile neutropenia. Percentages of pts with AEs leading to treatment discontinuation, reduction, or delay were 15.1%, 9.4%, and 26.4%, respectively. Conclusions: Eribulin is effective and safe as first-line therapy for aggressive taxane-resistant HER2[-] MBC pts.