Novel Androgen Receptor Modulator, Enobosarm, Enters Breast Cancer Treatment Arena

By: Celeste L. Dixon
Posted: Monday, February 26, 2024

For the first time, a non–estrogen receptor (ER) hormonal treatment approach—with enobosarm, an oral selective androgen receptor modulator—has shown clinical advantage in ER-positive, androgen receptor–positive, HER2-negative breast cancer, according to the authors of a phase II study published in The Lancet Oncology. Beth Overmoyer, MD, of Dana-Farber Cancer Institute, Boston, and colleagues conducted the nine-country, randomized, open-label study. Of an original 136 women treated, 102 were evaluable, and about 30% had a response at 24 weeks to this tumor-suppressing agent.

In fact, study coauthor Stephen N. Birrell, MBBS, PhD, of Burnside Hospital, Adelaide, South Australia, shared this comment in a University of Adelaide press release: “The fact that this drug is well tolerated also opens possibilities for its use in breast cancer prevention.”

The cancers of these patients, all postmenopausal, were either locally advanced or metastatic and had been previously treated. The patients were stratified between 2015 and 2017 by their immediately preceding endocrine therapy and the presence of bone-alone metastasis. These women were randomly assigned to receive 9 mg (n = 50) or 18 mg (n = 52) of oral enobosarm daily.

The median follow-up was 7.5 months. At 24 weeks, 16 of 50 patients (32%) in the 9-mg group and 15 of 52 patients (29%) in the 18-mg group had a clinical benefit. The data are “very promising,” Dr. Overmoyer said in a press release. “The study supports further investigation of enobosarm in earlier stages of breast cancer as well as in combination with targeted therapies, such as [the CDK4/6 inhibitor] ribociclib.”

Specifically, of the original group, 6 of 75 patients (8%) who received 9 mg and 10 of 61 patients (16%) who received 18 mg of enobosarm reported grade 3 or 4 drug-related adverse events, most frequently increased hepatic transaminases, hypercalcemia, and fatigue. The team believes that antiandrogen therapies may prove less toxic than antiestrogen therapies in the up to 80% of breast cancers that are ER-positive.

Disclosure: For full disclosure of the study authors, visit TheLancet.com.

The Lancet Oncology