Phase II study of apatinib plus exemestane in estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer.

"Disclosure statement No potential conflict of interest was reported by the authors."

"The included patients aged 18–70 years and were pathologically diagnosed as MBC, with ER+ (+, >10%) and HER2–. HER2- was defined as no staining or scores of 1+ by immunohistochemistry (IHC), and cases with 2+ by IHC were confirmed absence of HER2 gene amplification by fluorescence in situ hybridization (FISH). Patients were either postmenopausal women or receiving ovarian suppressive therapy. All patients had experienced treatment failure with previous anastrozole or letrozole, defined as disease recurrence or metastasis during or within one year after the end of adjuvant endocrine therapy, or progression during endocrine therapy in MBC. Chemotherapy or other endocrine therapy (tamoxifen, fulvestrant, toremifene, progesterone) for advanced disease were also allowed before inclusion. Patients who had previously taken exemestane were excluded unless they had experienced disease recurrence or metastasis one year after the end of adjuvant therapy with exemstane. The included patients had to have at least one measurable lesion, a life expectancy of no less than 3 months, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. They also had to have adequate hematologic, hepatic, and renal function, as indicated by hemoglobin ≥8 g/dL, absolute neutrophil count (ANC) ≥1.5 × 109/L, platelet count ≥75 × 109/L, total serum bilirubin ≤1.5 × upper limit of normal (ULN), AST/ALT ≤2.5 × ULN (≤5× ULN in case of liver metastases), and serum creatinine ≤1.0 × ULN (calculated creatinine clearance ≥50 mL/min). Patients with symptomatic brain metastases, uncontrolled hypertension, serious cardiovascular disease or previous treatment with angiogenesis inhibitors were excluded. At last, a total of 30 patients were enrolled in this study. All of the enrolled patients signed the informed consent and could be cooperative with medical workers. The study was approved by the Medical Ethics Committee of Guangxi Medical University Cancer Hospital (KS2017(05)) and was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study protocol has been registered in the Chinese Clinical Trial Registry (Identifier: ChiCTR-OIC-17010440)"