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

Abstract

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.

Therapeutic potential of tucidinostat, a subtype-selective HDAC inhibitor, in cancer treatment

“…Another phase II study reported the therapeutic efficacy of tucidinostat with cisplatin for advanced triple-negative breast cancer (TNBC). Single-agent platinum chemotherapy has been shown to induce an ORR of 31% (Waks and Winer, 2019), while the result in this trial showed an ORR of 26.7% (4/15), which indicates that the addition of tucidinostat did not improve the efficacy of cisplatin in the first-line treatment against advanced TNBC (Meng et al, 2021).…”

Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention

“…Women with TNBC were treated with tucidinostat/chidamide and cisplatin, 20 mg twice weekly for 2 weeks, and 75 mg/m 2 on a 21-day cycle, respectively. Despite the fact that this trial had several limitations, including a small sample size, nonrandomized character, and the un-selection of the enrolled patients, the combination of chidamide and cisplatin did not seem to exhibit a superior efficacy compared with classical cisplatin-based chemotherapy in treating advanced TNBC [274]. Additionally, romidepsin has been included in a phase I dose-escalation study (NCT01902225) in combination with liposomal doxorubicin, an anthracycline that intercalates within DNA base pairs and inhibits topoisomerase II to treat cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL).…”

Potential of histone deacetylase inhibitors in the control and regulation of prostate, breast and ovarian cancer

“…In metastatic advanced triple-negative breast cancer (TNBC) patients, a phase II single-arm clinical trial was done to examine the efficacy and safety of a combination treatment of tucidinostat/chidamide with cisplatin. Tucidinostat/chidamide and cisplatin, 20 mg twice weekly for 2 weeks and 75 mg/m2 on a 21-days cycle, were given to women with TNBC (Meng et al, 2021). Table 6 lists some of the most recent clinical trials for breast cancer treatment.…”