Background: At present, there is no standard second-line chemotherapy-based treatment in patients with HER2-negative MBC. Continued VEGF inhibition with bevacizumab is a new potential option in patients progressing to first line bevacizumab and chemotherapy. Eribulin is a non-taxane microtubule dynamics inhibitor, with a unique mechanism of action and suggested beneficial effects on tumor microenvironment and neoangiogenesis. This study evaluated efficacy and safety of eribulin plus bevacizumab as a novel second-line chemotherapy scheme, in patients progressing after first line paclitaxel and bevacizumab.

Methods: This is a multicenter, single-arm, Simon's two-stage, Phase II study. Patients with HER2-negative MBC progressing to paclitaxel and bevacizumab received eribulin (1.23 mg/m2 intravenously on Days 1 and 8 of every 21-day cycle) plus bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks intravenously), as second-line chemotherapy. The primary endpoint was the overall response rate (ORR), considered as sum of partial (PR) and complete response (CR), basing on the best overall response. The present safety and efficacy analyses, as planned per study design, refer to six cycles of treatment (18 weeks).

Results: Among the 61 patients enrolled in the study, 55 (90,2% ) were evaluable for efficacy. ORR (PR/CR) was 9.1% [95% confidence intervals (C.I.) 3.0 to 19.9]; stable disease (SD) rate was 63.6% [95% C.I. 49.6 to 76.2]; clinical benefit rate (CR/PR/SD) at 24 weeks was 35% [95% C.I. 22.0 to 49.1]. The median progression free survival was 6.3 months [95% C.I. 4.1 to 7.8 months]. Drugs-related adverse events (AEs) were: 49.5% related to eribulin, 7.7% related to bevacizumab, and 11.8% related to both the study drugs. The most common AEs were fatigue (9.9% of all AEs), paresthesia (6.5% of all AEs) and neutropenia (6.2% of all AEs). Quality of life was well preserved among the majority of patients.

Conclusions: The results of our trial suggest that continuing bevacizumab in combination with eribulin, beyond first line treatment with bevacizumab and paclitaxel, offers a reasonable therapeutic option for patients with HER2-negative MBC, without detrimentally affecting quality of life.

Citation Format: De Placido S, De Laurentiis M, Bruzzese D, Bernardo A, Baldini EE, Montesarchio V, Fabi A, Gamucci T, De Placido P, Russo S, Lauria R, De Santo I, De Angelis C, Del Mastro L, Giuliano M, Arpino G. A phase II single arm trial evaluating the efficacy and safety of eribulin in combination with bevacizumab for second-line treatment of human epidermal growth factor receptor 2 (HER2)–negative metastatic breast cancer (MBC) progressing after first-line therapy with bevacizumab and paclitaxel [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-21-13.