Exemestane + Tucidinostat

The combination of exemestane and tucidinostat is a therapeutic regimen used primarily for hormone receptor-positive breast cancer. Tucidinostat (formerly known as chidamide) is a selective histone deacetylase (HDAC) inhibitor that targets class I HDACs (HDAC1, 2, and 3) and class IIb HDAC10[1][5]. Exemestane is an aromatase inhibitor that reduces estrogen production, which is commonly used in hormone receptor-positive breast cancer treatment. ## Clinical Evidence The efficacy and safety of this combination were evaluated in the ACE trial (Chidamide and Exemestane), a randomized, double-blind, placebo-controlled phase 3 study conducted at 22 cancer centers in China[1][2]. The trial enrolled postmenopausal women with hormone receptor-positive, HER2-negative breast cancer whose disease had relapsed or progressed after at least one endocrine therapy[1]. In the ACE trial, patients received either 30 mg oral tucidinostat or placebo twice weekly, with all patients in both groups also receiving 25 mg oral exemestane daily[1]. The primary endpoint was investigator-assessed progression-free survival (PFS). Results showed that the combination of tucidinostat with exemestane significantly improved PFS compared to exemestane alone. The median PFS was 7.4 months in the tucidinostat group versus 3.8 months in the placebo group (p=0.033)[2][4]. Independent review committee assessment showed similar results with median PFS of 9.2 months versus 3.8 months (hazard ratio=0.713; p=0.024)[2]. However, updated results from the ACE study indicated that the PFS extension did not translate into overall survival (OS) benefit[2][4]. ## Safety Profile The most common adverse events associated with the tucidinostat plus exemestane regimen were hematological toxicities, particularly: - Neutropenia (grade 3 or 4 in 51.6% of patients in the tucidinostat group vs. 2.5% in the placebo group)[2] - Thrombocytopenia[5] - Leukopenia[5] - Anemia[5] Other common adverse events included fatigue, nausea/vomiting, and gastrointestinal disturbances[5]. Adverse events leading to treatment discontinuation occurred in 11.5% of patients in the tucidinostat group compared to 3.3% in the placebo group[2]. ## Regulatory Status Based on the ACE trial results, tucidinostat in combination with exemestane was approved by China's National Medical Products Administration (NMPA) in November 2019 for the treatment of hormone receptor-positive advanced breast cancer[2]. This made tucidinostat the first HDAC inhibitor approved globally for the treatment of solid tumors[5]. The combination is currently being studied in additional clinical settings, including as a neoadjuvant strategy in early-stage breast cancer[3][7].

Brand names

EpidazaAromasin

Other names

chidamide + exemestane