3895 - Phase III trial of chidamide, a subtype-selective histone deacetylase (HDAC) inhibitor, in combination with exemestane in patients with hormone receptor-positive advanced breast cancer

Background

Chidamide (CS055/Tucidinostat/Epidaza®) is an oral subtype-selective HDAC inhibitor. An exploratory clinical study has demonstrated the encouraging antitumor activity of chidamide in combination with exemestane in hormone receptor (HR)-positive advanced breast cancer (ABC) patients.

Methods

This randomized, double-blind, placebo controlled study involved postmenopausal patients with HR-positive, HER2-negative ABC failed to tamoxifen and/or nonsteroidal aromatase inhibitor. Eligible patients were randomly assigned (2:1) to two arms (chidamide 30 mg twice a week plus exemestane 25 mg daily or placebo plus exemestane). The primary endpoint was progression-free survival (PFS), assessed by investigator. Secondary endpoints were overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and safety.

Results

365 patients were enrolled at 22 centers in China, with 244 in the chidamide group and 121 in the placebo group. The median PFS was 7.4 months (95% confidence interval [CI], 5.5 to 9.2) with chidamide–exemestane and 3.8 months (95% CI, 3.7 to 5.5) with placebo–exemestane (hazard ratio for disease progression or death, 0.755; 95% CI, 0.582 to 0.978; P=0.0336). ORR was 18.4% and 9.1%（P=0.026）, and CBR was 46.7% and 35.5%（P=0.034）in the chidamide group and placebo group, respectively. Overall survival results were not mature at the time of the analysis. The most common grade 3 or 4 adverse events (AE) in the chidamide group were neutropenia (50.8% vs. 2.5% in the placebo group), thrombocytopenia (27.5% vs. 2.5%), and leucopenia (18.8% vs. 2.5%). Serious adverse events occurred in 51 (20.9%) patients in the chidamide group and 7 (5.8%) patients in the placebo group. No treatment related death was reported.

Conclusions

This is the first oral HDAC inhibitor combined with exemestane in a pivotal clinical study to demonstrate PFS benefit and manageable adverse effect in HR–positive ABC patients progressed after prior endocrine therapy.

Clinical trial identification

NCT02482753

Editorial Acknowledgement

The authors thank B. Wang, T. Liu, and J. Gao for their contributions to the study