Entinostat plus exemestane improves progression-free survival in Chinese patients

Patients with advanced hormone receptor (HR)–positive/HER2-negative breast cancer derived greater progression-free survival (PFS) benefit when treated with entinostat plus exemestane versus matched placebo, according to results from a Chinese, phase 3 study.

Entinostat is a potent, once weekly, orally bioavailable, class 1 selective histone deacetylase inhibitor. In breast cancer, disruption of oestrogen-mediated signalling results in acquired resistance to hormonal therapy. Entinostat is hypothesised to re-sensitise these cells to endocrine treatment. Prof. Binghe Xu (Chinese Academy of Medical Sciences, China) presented results of a double-blind, placebo-controlled, phase 3 (NCT03538171) trial evaluating the efficacy and safety of entinostat plus exemestane versus placebo plus exemestane in patients with HR-positive/HER2-negative advanced breast cancer who progressed on prior endocrine therapy [1].

A total of 354 patients were randomised 2:1 to entinostat (5 mg weekly) or placebo. Both groups received exemestane daily (25 mg). Treatment was given until disease progression or unacceptable toxicity. Median PFS was 6.32 months in patients treated with entinostat versus 3.72 months in patients treated with placebo (HR 0.74; P=0.021; see Figure). Median overall survival was not reached in both treatment arms (HR 0.75 in favour of entinostat). Overall response rates (ORR) were 15.7% and 10.1% and clinical benefit rates were 37.4% and 32.8%, respectively. Ad-hoc subgroup analysis of PFS showed that entinostat plus exemestane outperformed exemestane alone across all pre-specified subgroups, except for those who received prior fulvestrant. Regarding safety, the most common adverse events were hematologic toxicities, including neutropenia (43.8%), leukopenia (6.4%), thrombocytopenia (8.5%), and anaemia.

Figure: Progression-free survival of entinostat plus exemestane versus placebo plus exemestane treatment [1].



 

 

 

 

 

 

PFS, progression-free survival; HR, hazard ratio; CI, confidence interval.

“The entinostat plus exemestane combination significantly improved PFS compared with exemestane alone in patients with advanced, HR-positive/HER2-negative breast cancer that progressed after previous endocrine therapy,” concluded Prof. Xu. “Entinostat plus exemestane can offer meaningful clinical benefit in these patients.”

1. Xu B, et al. A randomized control phase III trial of entinostat, a once weekly, class I selective histone deacetylase inhibitor, in combination with exemestane in patients with hormone receptor positive advanced breast cancer. GS1-06, SABCS 2021 Virtual Meeting, 7–10 December.

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Posted on 31 January, 2022