# Chidamide (a Histone Deacetylase Inhibitor) Plus Abiraterone in Metastatic Castration‐Resistant Prostate Cancer (mCRPC): A Phase Ib Trial

## TL;DR

A Phase Ib trial tested chidamide plus abiraterone in mCRPC patients, showing tolerability and potential survival benefits.

## Contribution

This study provides preliminary evidence that chidamide combined with abiraterone may improve survival in mCRPC patients.

## Key findings

- The regimen showed limited Grade 3 toxicities and was well tolerated.
- Median progression-free survival was 3.7 months and median overall survival was 11.0 months.
- RNA sequencing indicated chidamide's potential to upregulate immune response pathways in tumor tissues.

## Abstract

The prognosis of metastatic castration‐resistant prostate cancer (mCRPC) remained unsatisfactory currently. Chidamide is a well tolerated, selective histone deacetylase (HDAC) inhibitor, but the efficacy in mCRPC remained uncertain. From August 2020 to October 2022, a total of 18 patients were enrolled. The primary endpoint was to assess the safety and the secondary endpoints including efficacy and biomarker analysis. The common adverse events (AEs) included anemia, anorexia, hypoalbuminemia, hyponatremia, nausea and fatigue. Grade 3 toxicities included anemia and thrombocytopenia, and no DLT was observed in this study. The median progression‐free survival (PFS) was 3.7 months (95% CI, 0.922–6.611 months), and the median OS was 11.0 months (95% CI, 2.232–19.768 months). The results of the RNA‐seq profile indicated the high immune cell infiltration and the upregulation of immune cell functions in tumor tissues was associated with the efficacy of chidamide, as revealed by GSEA and ssGSEA. Furthermore, chidamide has been demonstrated to upregulate immune response‐related pathways in CRPC cells. Our study suggested that chidamide plus abiraterone is well tolerated in mCRPC, and preliminary evidence suggests that it may improve the survival of patients with mCRPC. Furthermore, combining chidamide with immunotherapy could be another promising option for further enhancing its efficacy.

Metastatic castration‐resistant prostate cancer (mCRPC) remains challenging. This Phase Ib trial tested chidamide, a selective HDAC inhibitor, plus abiraterone in 18 patients. The regimen was well tolerated, with limited Grade 3 toxicities. Median PFS and OS were 3.7 and 11.0 months. RNA sequencing suggested chidamide's immunomodulatory role, supporting further exploration with immunotherapy.