Efficacy and exploratory biomarker analysis of entinostat plus exemestane in advanced or recurrent breast cancer: phase II randomized controlled trial.
Jpn J Clin Oncol
; 53(1): 4-15, 2023 Jan 06.
Article
em En
| MEDLINE
| ID: mdl-36398439
ABSTRACT
BACKGROUND:
We aimed to confirm the efficacy and safety of the oral histone deacetylase inhibitor entinostat in Japanese patients with hormone receptor-positive advanced/recurrent breast cancer and to explore potential biomarkers.METHODS:
This phase II, double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov; NCT03291886) was conducted at 28 Japanese sites (September 2017-July 2020; interim analysis cutoff April 2019). Patients with progression/relapse following non-steroidal aromatase inhibitors were randomized 11 to entinostat (5 mg/week) or placebo, plus exemestane (25 mg/day). Primary endpoint was progression-free survival; secondary endpoints included overall survival and safety. Exploratory biomarker outcomes included lysine acetylation, immune cell profiles, estrogen receptor 1 mutations and plasma chemokines.RESULTS:
Of 133 randomized patients, 131 (65 entinostat, 66 placebo) who received study drug were analyzed. Median (95% confidence interval) progression-free survival was 5.8 (3.2-7.8) months for entinostat and 3.3 (3.1-5.8) months for placebo (hazard ratio [95% confidence interval] 0.75 [0.50 - 1.14]; P = 0.189). Median overall survival was not reached in either group. Entinostat tended to prolong progression-free survival in patients aged ≥65 years, not endocrine resistant, or with estrogen receptor 1 Y537S mutation. Candidate biomarkers of efficacy (progression-free survival) included lysine acetylation in CD3+ cells, plasma interferon gamma-induced protein 10, dendritic cell CD86 expression, and CD4+ cell expression of human leukocyte antigen-DR and inducible T-cell co-stimulator. Safety was similar to non-Japanese populations; however, seven entinostat-treated patients (10.8%) had reversible lung injury.CONCLUSIONS:
In Japanese patients, the safety of entinostat plus exemestane was acceptable and progression-free survival was prolonged, although not significantly. Exploratory analyses identified potential biomarkers, including lysine acetylation, of efficacy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
1_ASSA2030
/
2_ODS3
Problema de saúde:
1_doencas_nao_transmissiveis
/
2_muertes_prematuras_enfermedades_notrasmisibles
Assunto principal:
Neoplasias da Mama
Tipo de estudo:
Clinical_trials
Limite:
Female
/
Humans
Idioma:
En
Revista:
Jpn J Clin Oncol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Japão