SABCS 2017: Enzalutamide and Exemestane in Hormone Receptor–Positive Breast Cancer
In the first reported randomized trial of the nonsteroidal antiandrogen enzalutamide in hormone receptor–positive metastatic breast cancer, the combination of enzalutamide and exemestane improved progression-free survival in patients with no prior endocrine therapy—but not in those who had received prior endocrine therapy—according to data presented by Ian Krop, MD, PhD, of Dana-Farber Cancer Institute, Boston, and colleagues, at the 2017 San Antonio Breast Cancer Symposium (SABCS; Abstract GS4-07). Enzalutamide is approved for the treatment of patients with metastatic castration-resistant prostate cancer.
The androgen receptor is expressed in the majority of hormone receptor–positive tumors, and androgen receptor signaling has been associated with resistance to endocrine therapy. In this placebo-controlled phase II trial, the researchers developed a gene signature–based biomarker indicating androgen receptor signaling may be predictive of response to enzalutamide.
Patients with hormone receptor–positive/HER2-normal advanced/metastatic breast cancer were randomized to receive either 50 mg of exemestane and 160 mg of enzalutamide or 25 mg of exemestane and placebo daily. Two parallel cohorts enrolled patients with no prior endocrine therapy (n=127) or one prior endocrine therapy (n=120). In the cohort with no prior endocrine therapy, 39.4% were biomarker-positive, compared with 29.2% in the group who had received prior endocrine therapy.
Statistically significant improvement in median progression-free survival was observed only in the biomarker-positive population with no prior endocrine therapy: 16.5 months for those who received exemestane and enzalutamide versus 4.3 months for those who received exemestane and placebo, the investigators reported.