Anlotinib has good efficacy and low toxicity: a phase II study of anlotinib in pre-treated HER-2 negative metastatic breast cancer
Nanlin Hu, Yiran Si, Jian Yue, Tingting Sun, Xue Wang, Zhuqing Jia, Songlin Gao, Qiao Li, Yang Shao, Jiayu Wang, Yang Luo, Fei Ma, Binghe Xu, Peng Yuan
Abstract
OBJECTIVE: Anlotinib is a novel tyrosine kinase inhibitor blocking angiogenesis. This study was performed to assess the efficacy and safety of anlotinib in patients with metastatic breast cancer. METHODS: Patients with HER2-negative breast cancer, who were pre-treated with anthracycline or taxanes in a neoadjuvant, adjuvant, or metastatic setting, and had treatment failure after at least one prior chemotherapy regimen in the metastatic setting were enrolled. Anlotinib was administered at 12 mg daily for 14 days in a 21-day cycle until disease progression or unacceptable toxicity occurred. Simultaneously, 5-10 mL of venous blood was collected to perform circulating tumor DNA (ctDNA) testing every 2 treatment cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), progression-free survival (PFS), overall survival, safety, and biomarkers. RESULTS: Twenty-six eligible patients were enrolled, with a median age of 56 (30-75) years. The median follow-up time was 10.5 months. The ORR was 15.4%, the DCR was 80.8%, and the median PFS was 5.22 months (95% confidence interval 2.86-6.24). Fourteen (53.8%) patients survived for more than 10 months. The changes in the detectable ctDNA variant allele frequency were consistent with the tumor response. The most common treatment-related adverse events were hypertension (57.7%), thyroidstimulating hormone elevation (34.6%), and hand-foot syndrome (23.1%). CONCLUSIONS: Anlotinib showed objective efficacy with tolerable toxicity in heavily pre-treated, metastatic HER2-negative breast cancer. The dynamic changes in the ctDNA variant allele fraction may be predictive of the tumor response.