In a phase II trial (Study G200802) reported in The Lancet Oncology, Palmieri et al found that the novel selective androgen receptor (AR) modulator enobosarm was active in previously treated patients with AR-positive, estrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer.
Study Details
In the international open-label trial, 136 eligible patients with previously treated locally advanced or metastatic disease were randomly assigned between September 2015 and November 2017 to receive oral enobosarm at either 9 mg/d (n = 72) or 18 mg/d (n = 64). Treatment continued until disease progression, unacceptable toxicity, or for up to 24 months. The primary endpoint was clinical benefit rate at 24 weeks in patients with centrally confirmed AR-positive disease (evaluable population; n = 50 in 9-mg group and n = 52 in 18-mg group). In the evaluable population, more patients in the 18-mg group had de novo metastatic disease (27%) vs those in the 9-mg group (12%).
KEY POINTS
- Clinical benefit was achieved in 29% of patients in the 18-mg group and 32% of patients in the 9-mg group.
- Median progression-free survival was 4.2 months and 5.6 months, respectively.
Clinical Benefit
Median follow-up was 7.5 months (interquartile range [IQR] = 2.9–14.1 months). At 24 weeks, clinical benefit was observed in 16 (32%, 95% confidence interval [CI] = 20%–47%) of 50 evaluable patients in the 9-mg group and in 15 (29%, 95% CI = 17%–43%) of 52 evaluable patients in the 18-mg group. Among patients with baseline measurable disease, objective response at 24 weeks was observed in 0 (0%) of 34 patients in the 9-mg group and 1 (2%) of 52 in the 18-mg group. Median progression-free survival was 5.6 months (IQR = 2.8 months to not reached) in the 9-mg group and 4.2 months (IQR = 2.7–11.8 months) in the 18-mg group.
Adverse Events
Among 136 patients in the safety population, grade 3 or 4 treatment-related adverse events occurred in 8% of the 9-mg group and 16% of the 18-mg group, most commonly increased transaminases (4% vs 3%), hypercalcemia (3% and 3%), and fatigue (1% and 3%). Adverse events led to death in one patient in the 9-mg group (due to acute kidney failure) and three patients in the 18-mg group (due to hypertension and cardiac failure; anemia and bone marrow failure; and sepsis, respectively); none of the deaths were considered related to treatment.
The investigators concluded, “Enobosarm has antitumor activity in patients with ER-positive, HER2-negative advanced breast cancer, showing that AR activation can result in clinical benefit, supporting further clinical investigation of selective AR activation strategies for the treatment of AR-positive, ER-positive, HER2-negative advanced breast cancer.”
Carlo Palmieri, MBBS, PhD, of the Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular, and Integrative Biology, the University of Liverpool, UK, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by GTx. For full disclosures of the study authors, visit thelancet.com.
