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

Chidamide is an oral subtype-selective histone deacetylase inhibitor that has been used as an anti-cancer agent. This study evaluated the efficacy and safety of chidamide plus fulvestrant in the treatment of HR-positive and HER2-negative advanced breast cancer. Eligible patients were women between the ages of 18–75 with HR + /HER2- advanced invasive breast cancer, whose disease relapsed or progressed after endocrine therapy with or without a CDK4/6 inhibitor (CDK4/6i). Eligible patients were treated with oral chidamide (30 mg twice weekly) plus intramuscular fulvestrant (500 mg on days 1 and 15 of cycle one, and then on day one of each subsequent 28 day cycle) until disease progression or toxicity related intolerance. Premenopausal women received a concomitant GnRH analogue. The primary endpoint was progression-free survival. Between Mar 19, 2021, and Mar 20, 2024, a total of 33 patients were enrolled. Of these, 30 patients who completed at least one post-baseline tumor assessment were included in the efficacy analysis. The median age was 54.5 years (range 31–70), with all 30 (100%) patients having an Eastern Cooperative Oncology Group Performance Status of 1. Visceral metastases were present in 80% (n = 24) of cases, and 50% (n = 15) exhibited metastases in > 3 anatomical sites. The median number of prior treatments was 2 (range 1–4). In total, 40% (n = 12) had undergone prior CDK4/6i therapy. The median progression-free survival for the entire cohort was 6.3 months (95% CI 5.0–9.0). The objective response rate (ORR) was 10%, with a disease control rate (DCR) of 83.3% (partial response + stable disease) and a clinical benefit rate (CBR) of 23.3%. Treatment related adverse events of any grade occurred in 30 (100%) patients, of those 9 (30%) were ≥ grade 3. The most frequent hematologic toxicities included leukopenia (all-grade: 67%; grade 3–4: 19%), followed by neutropenia (all-grade: 47%; grade 3–4: 19%) and thrombocytopenia (all-grade: 40%; grade 3–4: 6%). No treatment-related deaths occurred. Chidamide combined with fulvestrant showed encouraging antitumor activity and tolerable toxicity in pts with HR + /HER2- advanced breast cancer that had progressed after previous endocrine therapy. Trial registration ChiCTR2100044282, registered on March 14th 2021.