Entinostat plus exemestane improves PFS in hormone receptor-positive advanced breast cancer
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The addition of entinostat to exemestane improved PFS for patients with hormone receptor-positive, HER2-negative advanced breast cancer, according to randomized phase 3 study results presented at San Antonio Breast Cancer Symposium.
“The oral histone deacetylase inhibitor entinostat [SNDX-275, Syndax] has been investigated globally in more than 50 clinical trials as monotherapy and in combination with other agents,” Binghe Xu, MD, PhD, professor of medical oncology at Chinese Academy of Medical Sciences, said during a presentation. “Entinostat was designed to resensitize breast cancer cells to endocrine therapy.”
The trial included 354 pre- or post-menopausal women with advanced hormone receptor-positive, HER2-negative advanced breast cancer who had progressed on prior endocrine therapy.
Researchers randomly assigned 235 patients (median age, 53 years) to once-weekly oral entinostat dosed at 5 mg plus once-daily oral exemestane dosed at 25 mg. The other 119 patients (median age, 51 years) received placebo plus exemestane. Treatment continued until disease progression or intolerable toxicity.
PFS served as the primary outcome. Secondary outcomes included OS, objective response rate, clinical benefit rate and safety.
Results showed longer median PFS among patients assigned entinostat vs. placebo in the full analysis set (6.32 months vs. 3.72 months; HR = 0.74; 95% CI, 0.58-0.96) and the per-protocol set (7.34 months vs. 3.72 months; HR = 0.7; 95% CI, 0.53-0.91).
“[Median] OS was not yet reached in either group, but we expect to see good OS results within the next year,” Xu said.
Researchers reported numerically higher ORR and clinical benefit rates with entinostat per independent review committee and investigator assessment. The difference in clinical benefit rate per investigator assessment reached statistical significance (45.1% vs. 31.9%; P = .022).
A higher percentage of patients assigned entinostat experienced grade 3 (55.7% vs. 10.1%) or grade 4 (4.3% vs. 2.5%) treatment-related adverse events.
Researchers reported eight (3.4%) grade 5 toxicities in the entinostat group — five of which were deemed related to treatment — and one (0.8%) in the placebo group.
Hematologic adverse events that occurred more frequently among entinostat-treated patients included neutropenia (all grade, 73.2% vs. 3.4; grade 3/grade 4, 43.8% vs. 0.8%), leukopenia (all grade, 63.8% vs. 5%; grade 3, 6.4% vs. 0%) and thrombocytopenia (all grade, 66.8% vs. 12.6%; grade 3/grade 4, 8.5% vs. 0.8%). Hematologic toxicities were mostly asymptomatic and manageable with supportive care, Xu said.
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Xu B, et al. Abstract GS1-06. Presented at: San Antonio Breast Cancer Symposium; Dec. 7-10, 2021; San Antonio.
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