Key Points
• Conclusion/Relevance: “The combination of exemestane and entinostat did not improve survival in AI-resistant advanced HR-positive, HER2-negative breast cancer.”
• In this multicenter, randomized, double-blind, placebo-controlled phase III study (i.e., E2112) involving 608 women and men exhibiting advanced HR-positive, HER2-negative breast cancer, with disease progression following treatment with nonsteroidal aromatase inhibitor (AI). The treatment arm received exemestane 25 mg by mouth once daily and entinostat (EE), and the control arm received placebo (EP) 5 mg by mouth once weekly. Primary outcomes were PFS and OS.
• “The oncology literature has indicated that positive phase II data are not necessarily replicated in the phase III setting, highlighting the importance of careful phase III study design. E2112 did not meet its primary objective,” the authors wrote. “This was despite robust supportive preclinical data in AI-resistant breast cancer mouse models, and data from the ENCORE301 randomized phase II study, which reported both a PFS and OS improvement in advanced endocrine-resistant breast cancer.”
• Strengths of the current study include strong preclinical and clinical rationale, adequate power, and PFS and OS endpoints.
• “Although the study did not meet its primary objective, the data and biospecimens collected provide a rich resource for further investigation of prognostic and predictive factors in endocrine-resistant advanced breast cancer,” wrote the authors. They noted that because 35% of patients had been administered previous CDK inhibitors the results are relevant to current standards of managing AI-resistant HR-positive, HER2-negative advanced breast cancer.