The Efficacy and Safety of Anlotinib Combined With Fulvestrant in Patients With Advanced Breast Cancer

• Aged 18 years or older female；
• ECOG score 0-1;
• Life expectancy is not less than 12 weeks;
• Histology confirmed HR-positive and HER2-negative locally advanced or metastatic breast cancer;
• Premenopausal women have taken effective ovarian function suppression methods, such as drug suppression or ovariectomy;
• At least one objectively measurable breast cancer lesions according to RECIST 1.1 ;
• No more than one systemic chemotherapy for metastatic disease;
• Disease relapse within 12 months after at least 24 months endocrine adjuvant therapy, or disease progress after at least 6 months endocrine salvage therapy;
• Normal function of main organs and bone marrow: Hemoglobin≥90g/L; Neutrophil count (ANC)≥1.5×109/L; Platelet count (PLT)≥80×109/L; Total bilirubin≤1.5×ULN (upper limit of normal); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN (≤5×ULN if has liver metastasis); Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥60mL/min (Cockcroft-Gault formula);
• Sign the informed consent;

Exclusion Criteria:

• Have received prior fulvestrant or anti-angiogenic drug treatment, or known to be allergic to any excipients in the study;
• Visceral crisis;
• Uncontrolled or high-burden CNS metastases;
• Unable to swallow;
• Abnormal coagulation function;
• Tumor has invaded important blood vessels and may cause fatal bleeding;
• Pleural effusion or pericardial effusion that requiring repeated drainage;
• Hypertension that cannot be well controlled by a single antihypertensive drug;
• Unstable angina, myocardial infarction within 6 months, serious arrhythmias;
• The history of immunodeficiency, including HIV or other obtained or congenital immunodeficiency diseases, or a history of organ transplantation;
• Poorly controlled diabetes;
• Abnormal urine protein, and the 24-hour quantification suggests urine protein ≥1.0g;
• Bleeding constitution or medical history
• Unhealed wounds, ulcers or fractures;
• Have arterial/venous thrombotic events within 6 months, such as cerebrovascular accidents (including temporary ischemic attacks), deep vein thrombosis and pulmonary embolism;
• In other clinical trials of anti-tumor drugs simultaneously;
• Other concomitant disease or disability that endangers safety according to the judgment of investigator;