A randomized placebo controlled phase II trial evaluating exemestane with or without enzalutamide in patients with hormone receptor-positive breast cancer Journal Article
| Authors: | Krop, I.; Abramson, V.; Colleoni, M.; Traina, T.; Holmes, F.; Garcia-Estevez, L.; Hart, L.; Awada, A.; Zamagni, C.; Morris, P. G.; Schwartzberg, L.; Chan, S.; Gucalp, A.; Biganzoli, L.; Steinberg, J.; Sica, L.; Trudeau, M.; Markova, D.; Tarazi, J.; Zhu, Z.; O'Brien, T.; Kelly, C. M.; Winer, E.; Yardley, D. A. |
| Article Title: | A randomized placebo controlled phase II trial evaluating exemestane with or without enzalutamide in patients with hormone receptor-positive breast cancer |
| 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 1⁄4 127andcohort2,n1⁄4120).PFSwasnotimprovedineithercohortof the ITT population [HR, 0.82 (95% confidence interval (CI), 0.54-1.26); P 1⁄4 0.3631 for cohort 1 and HR, 1.02 (95% CI, 0.66-1.59); P 1⁄4 0.9212 for cohort 2]. In cohort 1, high levels of AR mRNA were associated with greater benefit of enzalutamide (Pinteraction 1⁄4 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 1⁄4 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. © 2020 American Association for Cancer Research. |
| Journal Title: | Clinical Cancer Research |
| Volume: | 26 |
| Issue: | 23 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2020-12-01 |
| Start Page: | 6149 |
| End Page: | 6157 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-20-1693 |
| PROVIDER: | scopus |
| PUBMED: | 32988969 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2021 -- Source: Scopus |
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