452P - A phase II trial of anlotinib and fulvestrant in patients with metastatic breast cancer previously treated with an aromatase inhibitor

Background

Fulvestrant is used after aromatase inhibitor (AI) failure in metastatic breast cancer but resistance develops quickly. We hypothesized that using anlotinib, a novel multi-target tyrosine kinase inhibitor, may delay fulvestrant resistance in patients (pts) and thus improve its efficacy. This single-arm, phase II trial aims to evaluate the efficacy and safety of the combined regimen in pts with HR-positive and HER2-negative, previously AI treated, locally advanced or metastatic breast cancer.

Methods

The key enrolled criteria were women aged 18 years or older of any menopausal status (premenopausal or perimenopausal women received ovarian function suppression), ECOG PS 0-1, histologically confirmed HR-positive and HER2-negative breast cancer, and disease relapse within 12 months after a more than 24 months AI adjuvant setting or disease progress after a more than 6 months AI metastatic setting. Eligible pts received 500 mg fulvestrant by intramuscular injection on days 1 and 15 of cycle one and then on day one of each subsequent cycle (28 days). Pts were also given 12 mg oral anlotinib once daily for 2 weeks, followed by a week off in a 21-day cycle. The primary endpoints is progression-free survival (PFS) and the secondary endpoints include overall response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.

Results

22 pts have been enrolled from Aug 25, 2021, to Apr 7, 2023. After a median follow-up time of 5.5 months (95% CI, 3.4-7.6), 21 pts had the confirmed best overall response assessments which inferred the ORR of 19.0% (PR in 4 pts. 95% CI, 5.4-41.9) and the DCR of 81.0% (PR in 4 pts and SD in 13 pts. 95% CI, 58.1-94.6). The median PFS was 7.6 months (95% CI 4.2-11.0) and the mOS has not reached. Any adverse events (AEs) were observed in 95.2% of pts, and the frequent AEs (incidence ≥ 10%) included hypertension (57.1%), proteinuria (23.8%), increased TSH (23.8%), hand-foot syndrome (19.0%), wight loss (19.0%), and thrombocytopenia (14.3%).

Conclusions

Anlotinib combined with fulvestrant showed a promising efficacy with an acceptable safety profile for patients with metastatic breast cancer previously treated with AI. Further results are expected.

Clinical trial identification

NCT05075512 October 12, 2021.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.