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Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer
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E2112: Randomized Phase III Trial of Endocrine Therapy Plus Entinostat or Placebo in Hormone Receptor-Positive

Roisin M Connolly1,2, Fengmin Zhao3, Kathy D Miller4

  • 1The Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
|August 6, 2021
PubMed
Abstract

Insights

Adding entinostat to exemestane did not improve survival for patients with advanced hormone receptor-positive, HER2-negative breast cancer resistant to endocrine therapy. Further research is needed for this patient population.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Endocrine therapy resistance is a major challenge in advanced breast cancer treatment.
  • Histone deacetylase inhibitors, like entinostat, are being investigated to overcome this resistance.

Purpose of the Study:

  • To evaluate the efficacy of combining entinostat with exemestane in patients with advanced hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer.
  • To assess the impact on progression-free survival (PFS) and overall survival (OS) in patients with aromatase inhibitor-resistant disease.

Main Methods:

  • A multicenter, randomized, double-blind, placebo-controlled phase III study (E2112) enrolled patients with advanced HR-positive, HER2-negative breast cancer progressing after nonsteroidal aromatase inhibitors (AIs).
  • Participants received either exemestane plus entinostat (EE) or exemestane plus placebo (EP).
  • Primary endpoints were PFS and OS, with safety and pharmacodynamic analyses as secondary endpoints.

Main Results:

  • The study enrolled 608 patients, with a median age of 63. Most patients had visceral disease and had progressed after prior AI treatment.
  • Median PFS was 3.3 months for EE versus 3.1 months for EP (hazard ratio = 0.87; P = .30).
  • Median OS was 23.4 months for EE versus 21.7 months for EP (hazard ratio = 0.99; P = .94). Common grade 3/4 adverse events in the EE arm included neutropenia and hypophosphatemia.

Conclusions:

  • The combination of exemestane and entinostat did not significantly improve PFS or OS in patients with AI-resistant advanced HR-positive, HER2-negative breast cancer.
  • The safety profile of the combination was consistent with known toxicities, with neutropenia being a notable adverse event.

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