Androgen receptor activation holds promise in ER+/HER2- breast cancer

The oral selective androgen receptor modulator enobosarm shows activity against ER-positive, HER2-negative advanced breast cancer, according to a phase II trial.

The trial involved 172 postmenopausal women with previously treated ER-positive, HER2-negative, locally advanced or metastatic breast cancer and an Eastern Cooperative Oncology Group performance status of 0–2. These patients were randomly assigned to receive either 9 mg or 18 mg of oral enobosarm daily. Treatment was administered for up to 24 months or until evidence of disease progression, occurrence of unacceptable toxicity, death, or discontinuation of study.

Clinical benefit, the primary endpoint, was assessed at 24 weeks in 102 participants (75 percent) with centrally confirmed androgen receptor (AR)-positive disease (ie, the evaluable population). Of the patients, 50 were in the 9-mg group (median age 60.5 years) and 52 were in the 18-mg group (median age 62.5 years). The median follow-up duration was 7.5 months.

At 24 weeks, clinical benefit was documented in 32 percent of participants in the 9-mg group and in 29 percent of those in the 18-mg group.

In terms of safety, grade 3 or 4 drug-related adverse events (AEs) occurred in 8 percent of participants in the 9-mg group and in 16 percent of those in the 18-mg group. Elevations in hepatic transaminases were the most frequent AE (4 percent and 3 percent, respectively), followed by hypercalcaemia (3 percent in both groups), and fatigue (1 percent and 3 percent, respectively).

Four patients died during the follow-up, including one in the 9-mg group and three in the 18-mg group. The deaths were deemed unrelated to the study drug.