medwireNews: Supplementing exemestane with the selective histone deacetylase inhibitor chidamide significantly prolongs the progression-free survival (PFS) of women with hormone receptor (HR)-positive, HER2-negative advanced breast cancer, phase III trial findings indicate.
Among the study participants – all of whom were postmenopausal and had progressed on prior endocrine therapy – median PFS was 7.4 months for the 244 patients who were randomly allocated to receive oral chidamide 30 mg every 2 weeks alongside daily exemestane 25 mg.
This was “almost double” the median 3.8 months that was achieved by the 121 participants who were instead given placebo plus exemestane, and gave a hazard ratio for progression or death of 0.755, reported Zefei Jiang (The 307th Hospital of Chinese People's Liberation Army, Beijing) at the ESMO 2018 Congress in Munich, Germany.
The objective response and clinical benefit rates were also higher in the chidamide than placebo group, at 18.4% versus 9.1% and 46.7% versus 35.5%, respectively.
And although the overall survival (OS) data were immature at the time of analysis, Jiang pointed out that the Kaplan–Meier curves started to separate at the 18-month mark and added that they hoped to report the OS findings in the next few months.
A higher proportion of chidamide-treated patients required a dose reduction or interruption due to adverse events (AEs) than their counterparts given placebo, at 33.2% versus 2.5% and 48.4% versus 4.1%, respectively, and this was also the case for AEs leading to discontinuation, with corresponding rates of 10.3% and 2.5%.
But Jiang noted that there were no treatment-related deaths during the course of the study.
The most common AEs of grade 3 or 4 in the chidamide group were hematologic toxicities, most often neutropenia (50.8%), thrombocytopenia (27.5%), and leukopenia (18.8%). By contrast, each of these AEs at this severity occurred in 2.5% of the placebo group.
Hypokalemia was the most frequently reported nonhematologic AE of grade 3 or 4 among patients receiving chidamide (6.1 vs 0.8% with placebo).
This is the first oral histone deacetylase inhibitor to show a PFS benefit and a manageable AE profile when combined with an aromatase inhibitor in a pivotal clinical study in this patient population, Jiang concluded.
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