Multicenter phase II study of Apatinib in non-triple-negative metastatic breast cancer

Abstract

BackgroundApatinib is a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2). This study was conducted to assess the efficacy and safety of apatinib in patients with non-triple-negative metastatic breast cancer who had received prior chemotherapy for their metastatic disease.MethodsThis multicenter, open-label, single arm study enrolled patients with non-triple-negative breast cancer, pretreated with anthracycline, taxanes and capecitabine, and who failed in the metastatic setting at least 1 and at most 4 prior chemotherapy regimens and at least one endocrine drug for hormone receptor-positive patients as well as at least one anti-Her2 drug for Her2-positive patients. 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. Apatinib was administered as 500 mg daily on days 1 through 28 of each 4-week cycle.Results38 patients were enrolled with a median age of 49 years (range, 35 to 62 years) and received apatinib for a median of 4 cycles (range from 0 to 10 cycles). 18 (47.4%) patients experienced dose reduction during treatment. The median relative dose intensity (relative to assigned dose for each cycle) was 82% (range, 45.0% to 100.0%). Median follow-up time was 10.1 months. Median PFS of all 38 patients was 4.0 months (95% confidence interval (CI), 2.8 m – 5.2 m). 36 patients were eligible for efficacy analysis. ORR was 16.7% (6/36). DCR was 66.7% (24/36). Median OS was 10.3 months (95% CI, 9.1 m – 11.6 m). The most common grade 3/4 treatment-related AEs were hypertension (20.5%), hand-foot syndrome (10.3%), and proteinuria (5.1%). Of three possibly drug-related SAEs recorded in the study, 2 (3.4%) deaths occurred within 28 days of last treatment and were both considered to be the result of disease progression. The other one was grade 2 diarrhea needing hospitalization.ConclusionsApatinib exhibited objective efficacy in heavily pretreated, metastatic non-triple-negative breast cancer with manageable toxicity, and it might be better to be tested in breast cancer with high angiogenesis dependency.Trial registrationClinicalTrials.gov: NCT01653561.

WITHDRAWN: The role of Apatinib combined with Paclitaxel (aluminum binding type) in drug-resistant ovarian cancer

“…Many research have shown that AP has showed strong tumor inhibition and tolerance in non-small cell lung cancer, gastric cancer, breast cancer and other malignant solid tumors [15][16][17], in OC patients, many achievements have also been made, in a phase II clinical study of recurrent epithelial ovarian cancer, the objective response rate (hereinafter referred to as ORR) of patients was 41.4%, and PFS was 14.5 months [18], in 2018, an article published in Lancet Oncol on the treatment of advanced ovarian cancer patients with AP and Etoposide showed that up to 54% of patients achieved remission [19], and in the same year, Jiuhuan found that the combination of AP and radiation paclitaxel can significantly inhibit tumor growth [20]. Therefore, we propose whether AP combined with nab-P can improve the therapeutic effect on platinum-relapsed patients.…”

Apatinib Inhibits Cell Proliferation and Induces Autophagy in Human Papillary Thyroid Carcinoma via the PI3K/Akt/mTOR Signaling Pathway

“…Apatinib has been approved as a safe and effective drug for patients with advanced gastric cancer for whom standard chemotherapy has failed (9,10). In addition, apatinib has shown antitumor effects in various types of solid tumors in a number of ongoing phase II and III clinical trials (11,12). Lin et al (13) reported that apatinib showed promising efficacy in a small number of patients with radioiodine-refractory differentiated thyroid cancer.…”

Apatinib targets both tumor and endothelial cells in hepatocellular carcinoma

“…Apatinib is a small‐molecular tyrosine kinase inhibitor that selectively binds and potently suppresses VEGFR‐2 and then blocks VEGFR‐2‐mediated angiogenesis . As one of the latest orally antiangiogenic agents, apatinib shows encouraging preclinical and clinical results in the treatment of various solid tumors . It has been approved for advanced gastric cancer after second‐line chemotherapy by China Food and Drug Administration .…”

“…16 As one of the latest orally antiangiogenic agents, apatinib shows encouraging preclinical and clinical results in the treatment of various solid tumors. [16][17][18][19][20][21] It has been approved for advanced gastric cancer after second-line chemotherapy by China Food and Drug Administration. 17 In addition, we have launched a phase II clinical trial of apatinib in advanced HCC.…”