Abstract Background: Chidamide is an oral subtype-selective histone deacetylase inhibitor previously utilized as an anti-cancer agent. The ACE study demonstrated that chidamide combined with exemestane significantly improved progression-free survival compared to placebo plus exemestane in patients with advanced, hormone receptor-positive(HR-positive), HER2-negative (HER2-) breast cancer who had experienced disease progression following prior endocrine therapy. This phase 2 study aimed to assess the efficacy and safety of chidamide in combination with fulvestrant for the treatment of HR-positive, HER2-negative advanced breast cancer that had progressed after previous endocrine therapy. Methods: Eligible patients were women aged 18 to 75 years with histologically confirmed HR+/HER2- advanced invasive breast cancer, whose disease had relapsed or progressed following at least one prior endocrine therapy, with or without a CDK4/6 inhibitor (CDK4/6i), administered in the advanced, metastatic, or adjuvant setting. Patients received oral chidamide (30 mg twice weekly for four consecutive weeks in a 4-week cycle) combined with intramuscular fulvestrant (500 mg on days 1 and 15 of cycle one, followed by day 1 of each subsequent 28-day cycle) until disease progression or intolerance. Premenopausal women were additionally treated with a concomitant GnRH analogue. The primary endpoint was progression-free survival (PFS),while secondary endpoints included overall response rate (ORR), duration of response (DoR), disease control rate (DCR), overall survival (OS), and safety. Results: Between March 8, 2021, and March 20, 2024, a total of 30 patients were enrolled. The median age was 54.5 years (range:31-70), with all 30 (100%) patients having an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 1. Additionally, visceral metastases were present in 80% (n = 24) of cases, and metastases involving more than three anatomical sites were observed in 50% (n = 15). The median number of prior chidamide treatments was two (range one to four). Overall, chemotherapy had been administered to 90% (n = 27) of the patients; primary endocrine resistance was noted in 10% (n = 3), and prior CDK4/6 inhibitor therapy had been utilized in 40% (n = 12).At the data cutoff date on September 15, 2024, five patients (17%) remained on the treatment regimen. Among all efficacy-evaluablepatients n= 30 the objective response rate (ORR) was reported as being at a level equivalent to ten percent while disease control rates stood at eighty-three point three. Conclusions: Chidamide combined with fulvestrant demonstrated promising antitumor efficacy and manageable toxicity in patients with HR+/HER2- advanced breast cancer who experienced disease progression following prior endocrine therapy. Citation Format: L. Zou, T. Xianjun, W. Li, X. Zeng, P. Deng, Y. Liu, T. Yang, X. Tan. Chidamide combined with fulvestrant in the treatment of HR-positive,HER2-negative advanced breast cancer after failure of previous endocrine therapy: A single-arm, single-center, phase 2 study abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-10-10.
Zou et al. (Tue,) studied this question.