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

by Selleckchem | Sep 08 2023

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.

Comments:

The study you mentioned is a single-center, open-label, phase II clinical trial that aimed to evaluate the efficacy and safety of eribulin mesylate, a microtubule dynamics inhibitor, alone or in combination with anlotinib, an oral small-molecule tyrosine kinase inhibitor, in patients with locally recurrent or metastatic HER2-negative breast cancer. The study was conducted in a Chinese hospital, and patients included had previously received anthracycline- or taxane-based chemotherapy.

A total of 80 patients were enrolled in the study, with 40 patients assigned to each treatment group. The primary endpoint of the study was investigator-assessed progression-free survival (PFS). The data were collected until August 10, 2022.

The results showed that the combination therapy of eribulin plus anlotinib resulted in a longer median PFS compared to eribulin monotherapy. The median PFS was 3.5 months (95% confidence interval [CI] 2.8-5.5 months) for eribulin monotherapy and 5.1 months (95% CI 4.5-6.9 months) for eribulin plus anlotinib. The hazard ratio was 0.56 (95% CI 0.32-0.98), indicating a statistically significant improvement in PFS with the combination therapy (P = 0.04).

The objective response rates, although not statistically significant, showed a trend towards improvement with the combination therapy (52.5% for eribulin plus anlotinib vs. 32.5% for eribulin monotherapy, P = 0.07). The disease control rates, which include both objective responses and stable disease, were significantly higher in the combination therapy group (92.5% for eribulin plus anlotinib vs. 67.5% for eribulin monotherapy, P = 0.01).

Subgroup analysis suggested that certain patient characteristics, such as age <50 years, Eastern Cooperative Oncology Group performance status score of 0, visceral metastasis, four or more previous treatment lines, hormone receptor negativity (triple-negative), and low HER2 expression, may benefit more from the combination treatment.

In terms of safety, the most common adverse events observed in both treatment groups were leukopenia, aspartate aminotransferase elevations, neutropenia, and alanine aminotransferase elevations.

Based on these findings, the study concluded that the combination of eribulin plus anlotinib could be considered as an alternative treatment option for patients with HER2-negative locally recurrent or metastatic breast cancer. However, it's important to note that further research, including larger clinical trials, is needed to confirm these results and determine the long-term efficacy and safety of this treatment combination.