A Prospective Study on Efficacy and Safety of Anlotinib Combined With Fulvestrant in Patients With HR-positive and HER2-negative, Secondary Endocrine-resistant, Locally Advanced or Metastatic Breast Cancer
The management of HR-positive, HER2-negative metastatic breast cancer includes endocrine monotherapy or combination regimens, both with benefit diminishing as resistance develops. Nowadays, various studies have demonstrated that estrogen interacts with many angiogenic pathways and is an important mechanism for resistance leading to the question of whether combination with antiangiogenesis and antiestrogen therapies could be an appropriate therapeutic modality. Anlotinib is a novel multi-target tyrosine kinase inhibitor that effectively inhibit VEGFR, FGFR, PDGFR, c-KIT, c-MET and RET. Previous studies have proven the efficacy of both anlotinib monotherapy and combination regimens in advanced breast cancer. This phase II study aims to preliminarily evaluate the efficacy and safety of anlotinib combined with endocrine therapy.
• 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;