A randomized trial of eribulin monotherapy versus eribulin plus anlotinib in patients with locally recurrent or metastatic breast cancer

Background: Eribulin mesylate is a novel, nontaxane, microtubule dynamics inhibitor. In this study, we assessed the efficacy and safety of eribulin versus eribulin plus the oral small-molecule tyrosine kinase inhibitor anlotinib in patients with locally recurrent or metastatic breast cancer.Patients and methods: In this single-center, open-label, phase II clinical study (NCT05206656) conducted in a Chinese hospital, patients with human epidermal growth factor receptor 2 (HER2)-negative, locally recurrent or metastatic breast cancer previously treated with anthracycline- or taxane-based chemotherapy were randomized (1 : 1) to receive eribulin alone or in combination with anlotinib. The primary efficacy endpoint was investigator-assessed progression-free survival (PFS).Results: From June 2020 to April 2022, a total of 80 patients were randomly assigned to either eribulin monotherapy or eribulin plus anlotinib combination therapy, with 40 patients in each group. The data cut-off was 10 August 2022. The median PFS was 3.5 months [95% confidence interval (CI) 2.8-5.5 months] for eribulin and 5.1 months (95% CI 4.5-6.9 months) for eribulin plus anlotinib (hazard ratio = 0.56, 95% CI 0.32-0.98; P = 0.04). The objective response rates were 32.5% versus 52.5% (P = 0.07), respectively, and disease control rates were 67.5% versus 92.5% (P = 0.01), respectively. Patients <50 years of age, with an Eastern Cooperative Oncology Group performance status score of 0, visceral metastasis, number of treatment lines of four or more, hormone receptor negative (triple-negative), and HER2 low expression appeared to benefit more from combined treatment. The most common adverse events in both groups were leukopenia (n = 28, 70.0%, patients in the eribulin monotherapy group versus n = 35, 87.5%, patients in the combination therapy group), aspartate aminotransferase elevations (n = 28, 70.0%, versus n = 35, 87.5%), neutropenia (n = 25, 62.5%, versus n = 31, 77.5%), and alanine aminotransferase elevations (n = 25, 62.5%, versus n = 30, 75.0%).Conclusion: Eribulin plus anlotinib can be considered an alternative treatment option for HER2-negative locally advanced or metastatic breast cancer.