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Background: 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. Methods: This study is a prospective, single-arm, open-label, phase II clinical trial. Eligible patients were women aged 18 years or older of any menopausal status (the premenopausals had to receive luteinising-hormone-releasing-hormone agonist at least 4 weeks before randomisation) and with ECOG status 0-1, who had HR-positive (estrogen receptor- and/or progesterone receptor-positive) and HER2-negative, secondary endocrine-resistant (defined as disease relapse within 12 months after at least 24 months endocrine adjuvant therapy, or disease progress after at least 6 months endocrine salvage therapy), locally advanced or metastatic breast cancer. Mainly exclusive criteria included the previous use of angiogenic inhibitors or fulvestrant, prior more than one line of chemotherapy, visceral crisis, and uncontrolled CNS metastases. Eligible patients were treated with oral anlotinib (12 mg once daily on days 1-14, repeated every 21 days) plus intramuscular fulvestrant (500 mg on days 1 and 15 of cycle one, and then on day one of each subsequent 28 days cycle) till disease progression or intolerant toxicity. The primary endpoints is progression-free survival (PFS) and the secondary endpoints include overall response rate (ORR), Clinical Benefit Rate (CBR), overall survival (OS), and safety. In the part of statistical analysis, 40 patients are required to have a 80% power to detect significant improvement in median progression-free survival from 5.8 (fulvestrant alone) to 10 (fulvestrant combined with anlotinib) months, if tested at a two-sided significance level of α=0.05. This study is currently enrolling patients and planned completion in July, 2023. Registration information: ChiCTR2100047080. Results: The trial is in progress. Conclusion: The trial is in progress. Citation Format: Xiaojia Wang, Jian Huang. A prospective phase II 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 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-27-02.
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