Anlotinib in combination with metronomic chemotherapy in HER2-negative metastatic breast cancer: an observational and retrospective study

Anti-angiogenesis offers an important treatment strategy for metastatic breast cancer (MBC). Metronomic chemotherapy (MCT) provides antiangiogenic effects without increased toxicities, making it good partner for antiangiogenic therapy. We conducted the present retrospective study to evaluate the efficacy and safety of anlotinib plus MCT for HER2 negative MBC. Patients with HER2 negative MBC who received metronomic chemotherapy (Vinorelbine (NVB), Capecitabine (CAPE), Etoposide (VP-16)) with anlotinib were retrospectively analyzed from Jan 2019 to Dec 2021. The primary end point was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. 48 patients with HER2 negative MBC were enrolled. 19 (39.6%) patients received NVB, 17 (35.4%) patients received CAPE and 12 (25.0%) patients received VP-16. The overall ORR and DCR were 8.3% (4/48) and 87.5% (42/48) respectively. The median PFS was 5.6 months (95% CI 4.3-7.0 months), and the median OS was 25.2 months (95% CI 20.2-30.1 months). The patients with age >= 50 (5.3 vs. 7.7 months, P = 0.014, HR = 0.407) and pathologic grade 1 or 2 (6.2 vs. 3.2 months, P = 0.023, HR = 2.471) had significantly longer PFS. The patients with hormone receptor (HR) positive (5.3 vs. 7.7 months, P = 0.004, HR = 0.206) and pathologic grade 1 or 2 (6.2 vs. 3.2 months, P = 0.020, HR = 3.882) had significantly longer OS. The incidence of all grades adverse events (AEs) was 56.3% (27/48) and grade 3-4 AEs was 12.5% (6/48). Within the context of real-world clinical practice, anlotinib in combination with metronomic chemotherapy provides a well-tolerated and effective treatment option for HER2-negative MBC, which warrants further investigation in the future.