A phase II trial of anlotinib combined chemotherapy as second-line and above therapy in HER2-negative advanced breast cancer.

e13140 Background: The group of HER2-negative accounts for about 75% of breast cancer and has limited response to chemotherapy. Anlotinib is a novel multitarget tyrosine kinase inhibitor targeting VEGFR, PDGFR, FGFR, and c-Kit. In this study, we assessed the efficacy and safety of anlotinib plus chemotherapy in second-line and above treatment of HER-2 negative advanced breast cancer. Methods: This open-label, single-arm, phase II study enrolled women aged 18-75 years with HER2-negative breast cancer who underwent at least one-line chemotherapy. All patients were treated with anlotinib (12mg, qd, administered orally on Days 1-14 of each 21 day cycle) in combination with investigator-selected chemotherapy. The primary endpoint evaluated in this study was the median progression-free survival (PFS). Secondary endpoints included the objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR) and safety. Results: From August 2022 to August 2023, 33 patients were enrolled in this study including 22(66.7%) HR+/HER2- patients and 11(33.3%) TNBC patients. After a median follow-up time of 11 months (95% CI, 5.8-16.2), the median PFS (mPFS) of the all patients was 8.6 months (95% CI 7.3-NA). In the HR+ and HR- populations, mPFS was 7.6 months versus 9.5 months (HR,0.376 95%CI 0.12-1.13, p=0.072), respectively. All the patients had the confirmed best overall response assessments, no patient achieved complete response (CR); 11(33.3%) patients got partial response (PR) and 19(57.6%) patients achieved stable disease (SD). ORR was 33.3% (95% CI 18.0-51.8), DCR was 90.9% (95% CI 75.7-98.1) and CBR was 60.6% (95% CI 42.1-77.1). The most frequently observed adverse events were elevated triglycerides (78.8%), elevated blood sugar (63.6%), anemia (60.6%), elevated cholesterol (51.5%), elevated alanine aminotransferase (48.5%), and leukopenia (48.5%). Dose reductions due to adverse events occurred in 7 (21.2%) patients. Conclusions: Anlotinib combined with chemotherapy showed a promising efficacy with an acceptable safety profile for second-line and above patients with HER2-negative metastatic breast cancer. Further studies enrolling more patients are still needed.