Chidamide (a Histone Deacetylase Inhibitor) Plus Abiraterone in Metastatic Castration-Resistant Prostate Cancer...

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.