Abstract P3-01-12: Chidamide combined with fulvestrant in the treatment of HR-positive and HER2-negative advanced breast cancer after failure of previous endocrine therapy:A single-arm, single-center, phase 2 study
Authors: Li Wei , Zou La , Zeng Xiaohua 
Published: March 2023

Background: Chidamide is an oral subtype-selective histone deacetylase inhibitor. The ACE study demonstrated that chidamide plus exemestane improved progression-free survival compared with placebo plus exemestane in patients (pts) with advanced, HR-positive, HER2-negative breast cancer that progressed after previous endocrine therapy. This phase 2 study aims to evaluate the efficacy and safety of chidamide plus fulvestrant in the treatment of HR-positive and HER2-negative advanced breast cancer that had progressed after previous endocrine therapy.

Methods: Eligible pts were women aged 18-75 years with histologically confirmed HR-positive, HER2-negative, advanced invasive breast cancer, whose disease relapsed or progressed after at least one endocrine therapy with or without a CDK4/6i (either in the advanced or metastatic or adjuvant setting). Eligible pts were treated with oral chidamide (30mg twice a week for 4 consecutive weeks in a 4-week cycle) plus intramuscular fulvestrant (500 mg intramuscular injection; on days 0, 14, 28, then every 28 days thereafter) till disease progression or intolerant toxicity. Premenopausal women received a concomitant GnRH analogue. The primary endpoint is progression-free survival (PFS) and the secondary endpoints include overall response rate (ORR), duration of response (DoR), disease control rate (DCR), overall survival (OS), and safety.

Results: Between Mar 8, 2021 and May 20, 2022, a total of 18 pts were enrolled. Median age was 53.5 years (range 45-67), 18 (100%) pts had ECOG PS 1, 16 (89%) had visceral disease, 14 (78%) pts had prior treatments with the median lines of 2, including 12 (86%) received endocrine treatment, and 11 (79%) received chemotherapy in the metastatic setting. At data cutoff (Jul 3, 2022), 8 (44.4%) pts were still receiving the drug regimen. The median PFS was 7.2 (95% CI, 5.83-8.49) months. In the 17 efficacy evaluable pts, the ORR was 17.6% (95% CI, 3.8%-43.4%), DCR was 88.2% (95% CI, 63.6%-98.5%). Treatment related adverse events (TRAEs) of any grade occurred in 18 (100%) pts, in which 4 (22.2%) were ≥ grade 3. The most common grade 3 or 4 TRAEs (incidence ≥10%) were leucopenia (22.2%), and neutropenia (22.2%). No treatment-related deaths occurred. The trial is ongoing.

Conclusions: Chidamide combined with fulvestrant showed encouraging antitumor activity and tolerable toxicity in pts with HR-positive and HER2-negative advanced breast cancer that had progressed after previous endocrine therapy. Clinical trial information: ChiCTR2100044282. Research Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd and Shenzhen Chipscreen Biosciences Co., Ltd.

Baseline characteristics

Citation Format: Wei Li, La Zou, Xiaohua Zeng. Chidamide combined with fulvestrant in the treatment of HR-positive and HER2-negative advanced breast cancer after failure of previous endocrine therapy:A single-arm, single-center, phase 2 study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-01-12.