A randomized placebo controlled phase II trial evaluating exemestane with or without enzalutamide in patients with hormone receptor-positive breast cancer

Ian Krop, Vandana Abramson, Marco Colleoni, Tiffany Traina, Frankie Holmes, Laura Garcia-Estevez, Lowell Hart, Ahmad Awada, Claudio Zamagni, Patrick G. Morris, Lee Schwartzberg, Stephen Chan, Ayca Gucalp, Laura Biganzoli, Joyce Steinberg, Lorenzo Sica, Maureen Trudeau, Denka Markova, Jamal Tarazi, Zhou ZhuThomas O'Brien, Catherine M. Kelly, Eric Winer, Denise A. Yardley

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To determine whether the androgen receptor (AR) inhibitor, enzalutamide, improves effectiveness of endocrine therapy (ET) in hormone receptor-positive (HRþ) breast cancer. Patients and Methods: In this phase II trial, patients with HRþ/HER2 normal advanced/metastatic breast cancer were randomized 1:1 to exemestane 25 mg with placebo or exemestane 50 mg with enzalutamide 160 mg daily (NCT02007512). Two parallel cohorts enrolled patients with 0 (cohort 1) or 1 (cohort 2) prior ET for advanced disease. Progression-free survival (PFS) was the primary endpoint in the intent-to-treat (ITT) population of each cohort. Biomarkers were evaluated in an exploratory analysis. Results: Overall, 247 patients were randomized (cohort 1, n ¼ 127andcohort2,n¼120).PFSwasnotimprovedineithercohortof the ITT population [HR, 0.82 (95% confidence interval (CI), 0.54-1.26); P ¼ 0.3631 for cohort 1 and HR, 1.02 (95% CI, 0.66-1.59); P ¼ 0.9212 for cohort 2]. In cohort 1, high levels of AR mRNA were associated with greater benefit of enzalutamide (Pinteraction ¼ 0.0048). This effect was particularly apparent in patients with both high levels of AR mRNA and low levels of ESR1 mRNA [HR, 0.24 (95% CI, 0.10-0.60); P ¼ 0.0011]. The most common any grade adverse events in the enzalutamide arms were nausea (39%) in cohort 1 and fatigue (37%) in cohort 2. Conclusions: Enzalutamide with exemestane was well tolerated. While PFS was not improved by the addition of enzalutamide to exemestane in an unselected population, ET-naive patients with high AR mRNA levels, particularly in combination with low ESR1 mRNA levels, may benefit from enzalutamide with exemestane.

Original languageEnglish
Pages (from-to)6149-6157
Number of pages9
JournalClinical Cancer Research
Volume26
Issue number23
DOIs
Publication statusPublished - Dec 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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