Jiang Z, et al. - The effectiveness and safety of the combination of tucidinostat with exemestane were investigated in a randomized trial in a larger population of postmenopausal patients with advanced, hormone receptor-positive breast cancer. Findings revealed the achievement of improved progression-free survival with this combination vs placebo plus exemestane in these patients. The tucidinostat plus exemestane group experienced grade 3-4 hematological adverse events more commonly than the placebo plus exemestane group. For these patients, tucidinostat plus exemestane may serve as a new treatment option.

Methods

• At 22 specialist cancer centers in China, this randomized, double-blind, placebo-controlled, phase 3 ACE trial was conducted.
• Postmenopausal women (aged ≥60 years or aged <60 years if their serum follicle-stimulating hormone and estradiol concentrations were within postmenopausal ranges) with hormone receptor-positive, HER2-negative breast cancer, whose disease had relapsed or progressed after at least one endocrine therapy (either in advanced or metastatic or adjuvant setting), and who had at least one measurable lesion, adequate organ function, Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and adequate hematological and biochemical parameters, were eligible for inclusion.
• Using a dynamic randomization scheme via an interactive web-response system, researchers randomly assigned the patients (2:1) to receive 30 mg oral tucidinostat or placebo twice weekly; in addition, 25 mg oral exemestane was administered to all patients in both groups daily.
• Investigator-assessed progression-free survival was the primary endpoint.
• The full analysis set population, comprising all patients who received at least one dose of any study treatment was included in the efficacy analyses, and all patients who received at least one dose of any study treatment and for whom at least one safety case report form was available were included in the safety analyses.

Results

• Enrollment and random assignment of 365 patients were done from July 20, 2015 to June 26, 2017, with 244 to the tucidinostat group and 121 to the placebo group.
• Researchers followed-up the patients for median period of 13.9 months (IQR 9.8–17.5).
• In the tucidinostat group and the placebo group, the respective investigator-assessed median progression-free survival was 7.4 months (95% CI 5.5–9.2) and 3.8 months (3.7–5.5) (HR 0.75 [95% CI 0.58–0.98]; p=0.033).
• Neutropenia (124 [51%] of 244 patients in the tucidinostat group vs three [2%] of 121 patients in the placebo group), thrombocytopenia (67 [27%] vs three [2%]), and leucopenia (46 [19%] vs three [2%]) were the most common grade 3 or 4 adverse events in either group.
• Fifty-one (21%) of 244 patients in the tucidinostat group and seven (6%) of 121 patients in the placebo group experienced serious adverse events of any cause.
• Death related to treatment was not reported.