Eribulin in combination with bevacizumab as second-line treatment for HER2–negative metastatic breast cancer progressing after first-line therapy with paclitaxel and bevacizumab: a multicenter, phase II, single arm trial (GIM11-BERGI)

Background: Currently, there is no standard second-line chemotherapy-based treatment for patients with HER2-negative metastatic breast cancer (MBC). Continued VEGF inhibition with bevacizumab is an option in patients progressing to first-line bevacizumab and chemotherapy. Eribulin is a non-taxane microtubule dynamics inhibitor with a unique mechanism of action that has been shown to exert beneficial effects in the tumor microenvironment and on neoangiogenesis. We evaluated the efficacy and safety of eribulin plus bevacizumab in 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 each 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, considered as the sum of partial (PR) and complete response (CR) based on the best overall response (BORR).Results: Fifty-eight (95.1%) of the 61 patients enrolled in the study were evaluable for efficacy. The BORR was 24.6% (95% confidence intervals [CI], 14.5% to 37.3%). The CBR (i.e. the CR + PR + SD response that persisted for more than 24 weeks) was 32.8% (95% CI, 21.3% to 46.0%). The median progression-free survival was 6.2 months (95% CI, 4.0 to 7.8 months). Overall, adverse events (AEs) were clinically manageable and the most common were fatigue (9.9% of all AEs), paresthesia (6.5% of all AEs) and neutropenia (6.2% of all AEs). Moreover, 49.5% of AEs were related to eribulin, 7.7% to bevacizumab, and 11.8% to both drugs. Quality of life was well preserved in most patients.Conclusions: The results of this study suggest that continuing bevacizumab in combination with eribulin, beyond first line treatment with bevacizumab and paclitaxel is a reasonable therapeutic option for patients with HER2-negative MBC that exerts its effect without detrimentally affecting quality of life.Trial registration: clinicalTrial.gov: NCT02175446. Registered 26, June 2014. https://clinicaltrials.gov/ct2/show/NCT02175446