A phase 3 clinical trial reports that tucidinostat (Epidaza®, Chipscreen Biosciences Ltd) in combination with exemestane (Aromasin®, Pfizer Inc.) improves progression-free survival compared with exemestane alone in postmenopausal patients with advanced, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer experiencing disease progression following prior endocrine therapy.
Also known as chidamide, tucidinostat is an orally bioavailable subtype-selective histone deacetylase inhibitor. Exemestane is an aromatase inhibitor, a type of hormone therapy.
"In an exploratory study, the combination of tucidinostat with exemestane showed preliminary signs of encouraging anti-tumor activity in patients with advanced hormone receptor-positive breast cancer," state lead author Zefei Jiang, MD, Professor in the Department of Breast Cancer of The Fifth Medical Centre of Chinese PLA General Hospital in Beijing, and colleagues in their publication in The Lancet Oncology. "To build on these findings, we aimed to assess the efficacy and safety of this combination in a randomized trial in a larger population of postmenopausal patients with advanced, hormone receptor-positive breast cancer."
The ACE trial (NCT02482753) enrolled 365 postmenopausal women with HR-positive, HER2-negative breast cancer experiencing disease relapse or progression after at least one endocrine therapy. Participants were required to have one or more measurable lesions, adequate organ function, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and sufficient hematological and biochemical parameters. The double-blind, placebo-controlled study randomly assigned patients in a 2:1 ratio to receive 30 mg oral tucidinostat or placebo twice per week, in combination with daily 25 mg oral exemestane. The study's primary end point was progression-free survival. Patients were followed for a median of 13.9 months.
Tucidinostat/exemestane increased median progression-free survival compared with placebo/exemestane (7.4 vs 3.8 months). The most common grade 3/4 adverse events in either trial arm included neutropenia (51% of patients receiving tucidinostat vs 2% of patients receiving placebo), thrombocytopenia (27% vs 2%), and leucopenia (19% vs 2%). Twenty-one percent of patients in the tucidinostat/exemestane group experienced serious adverse events of any cause, compared with 6% of those in the placebo/exemestane group. No treatment-related deaths were reported.
The researchers emphasize the importance of their trial's results: "Tucidinostat plus exemestane could represent a new treatment option for these patients."
For More Information
Clinicaltrials.gov (2019). Trial of chidamide in combination with exemestane in patients with advanced breast cancer. NLM identifier: NCT02482753.
Jiang Z, Li W, Hu X, et al (2019). Tucidinostat plus exemestane for postmenopausal patients with advanced, hormone receptor-positive breast cancer (ACE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. [Epub ahead of print] DOI:10.1016/S1470-2045(19)30164-0
Image credit: Sheheryar Kabraji and Sridhar Ramaswamy. Courtesy of the National Cancer Institute, Dana-Farber Harvard Cancer Center at Mass General