Addition of Tucidinostat to Exemestane in Advanced Hormone Receptor–Positive Breast Cancer


Key Points

  • The addition of tucidinostat to exemestane significantly prolonged progression-free survival.
  • The combination was associated with a greater incidence of grade 3 or 4 hematologic toxicity.

In the Chinese phase III ACE trial reported in The Lancet Oncology, Jiang et al found that the addition of the oral histone deacetylase inhibitor tucidinostat to exemestane improved progression-free survival in postmenopausal women with advanced hormone receptor (HR)-positive breast cancer whose disease had progressed after prior endocrine therapy.

Study Details

The double-blind, multicenter trial included 365 women with HR-positive, HER2-negative breast cancer that relapsed or progressed after at least one endocrine therapy in the advanced or metastatic or adjuvant setting. Patients were randomly assigned 2:1 between July 2015 and June 2017 to receive tucidinostat 30 mg twice weekly plus exemestane 25 mg daily (n = 244) or placebo plus exemestane (n = 121).

The primary endpoint was investigator-assessed progression-free survival.

Progression-Free Survival

Median duration of follow-up was 13.9 months. Median progression-free survival was 7.4 months in the tucidinostat group vs 3.8 months in the placebo group (hazard ratio [HR] = 0.75, P = .033). Objective response was observed in 18% vs 9% of patients. Overall survival data were not mature at data cutoff, at which time death had occurred in 23% of the tucidinostat group and 26% of the placebo group.

Adverse Events

The most common grade 3 or 4 adverse events in the tucidinostat group were neutropenia (51% vs 2% in placebo group), thrombocytopenia (27% vs 2%), and leukopenia (19% vs 2%). Serious adverse events occurred in 21% vs 6% of patients. No treatment-related deaths were observed.

The investigators concluded, “Tucidinostat plus exemestane improved progression-free survival compared with placebo plus exemestane in patients with advanced, hormone receptor–positive, HER2-negative breast cancer that progressed after previous endocrine therapy. Grade 3–4 haematological adverse events were more common in the tucidinostat plus exemestane group than in the placebo plus exemestane group. Tucidinostat plus exemestane could represent a new treatment option for these patients.”

Zefei Jiang, MD, of the Department of Breast Cancer, The Fifth Medical Centre of Chinese PLA General Hospital, Beijing, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Chipscreen Biosciences. For full disclosures of the study authors, visit

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