A phase II, single-arm study of apatinib and oral etoposide in pretreated metastatic HER2-negative breast cancer.

Abstract

1076 Background: There is no standard treatment strategy for patients with locally advanced or metastatic breast cancer suffering progression after one prior chemotherapy with metastasis setting. Apatinib is a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2). Etoposide is a highly active chemo-drug in the treatment of advanced breast cancer, both as a single agent or in combination regimens, and is well tolerated, with a low incidence of severe toxicity. This study is performed to assessed the efficacy and safety of apatinib and oral etoposide in patients with HER2 negative locally advanced or metastatic breast cancer for whom at least one lines of prior chemotherapy had failed. Methods: This open-label, single arm study enrolled patients with HER2-negative breast cancer, pretreated with anthracycline, taxanes, and who failed in the metastatic setting at least one prior chemotherapy regimens and at least one endocrine drug for hormone receptor-positive patients. Apatinib was administered 425/500mg daily according to patients ECOG(Eastern Cooperative Oncology Group) status, oral etoposide was administered 50mg/m2 for first 10 days in a 21-days cycle. The primary end point of this study was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. The treatment duration is until disease progression or intolerability of apatinib or oral etoposide. Results: 20 eligible patients were enrolled in this, open-label, single arm study and received apatinib and oral etoposide with a median age of 54 years old(range 36 to 66 years). Median follow-up time was 11months. 20 patients were eligible for efficacy analysis. Median PFS was 5.6 months (95% confidence interval (CI), 4.01 m – 8.42 m). ORR was 20% (4/20). DCR was 70% (14/20). Median OS was 11.2 months (95% CI, 9.6 m – 14.95 m). The most common grade 3/4 treatment-related AEs were hypertension (30%), and proteinuria (5%), nausea (5%). 35%(7/20) patients had dose reduction because of adverse events, after that all adverse events can return to less than 2 grade. Conclusions: Apatinib with oral etoposide exhibited objective efficacy in pretreated, metastatic HER2-negative breast cancer with manageable toxicity. Prospective studies enrolling more patients are needed. Clinical trial information: NCT03535961.