Phase II study of chidamide in combination with cisplatin in patients with metastatic triple-negative breast cancer

Background: Platinum-based regimens are the mainstay treatments for advanced triple-negative breast cancer (TNBC). Preclinical studies have shown that the histone deacetylase (HDAC) inhibitor chidamide induced antitumor effects in TNBC, and chidamide plus chemotherapy was shown to be tolerable in several malignancies. This study sought to investigate the efficacy and safety of a combination treatment of chidamide and cisplatin in metastatic TNBC patients. Methods: In this phase II, single-arm study, women with metastatic TNBC were administered chidamide (20 mg twice weekly for 2 weeks on a 21-day cycle) and cisplatin (75 mg/m(2) on a 21-day cycle). The primary endpoint was the objective response rate (ORR) by RECIST 1.1. The severity of adverse events was measured by the CTCAE 4.03. Results: Sixteen patients were enrolled in this study. Of these, 15 were available for evaluation. In these 15 patients, confirmed objective responses were seen in 4 patients [26.67%, 95% confidence interval (CI): 10.9%, 51.95%]. The ORRs did not meet the predefined criteria (of a response by at least 5 of the 15 patients); thus, the study remained at stage I. The median progression- free survival (PFS) was 9.8 weeks; 4 patients had a PFS of >25 weeks. In relation to the treatment-related AEs >= grade 3, >2 patients had neutropenia (33%), thrombocytopenia (20%), leucopenia (20%), and vomiting (20%). Conclusions: The addition of chidamide did not improve the efficacy of cisplatin in the first-line treatment against advanced TNBC; thus, the phase II clinical trial did not progress any further. Our study appears to be the first to investigate the HDAC inhibitor in TNBC patients and showed disappointing results, which should inform future studies. Future research on cisplatin-based combination treatments for TNBC should consider selecting patients based on predictive biomarkers to increase the clinical benefits.