Selective androgen receptor agonist may benefit some breast cancer patients
A subset of patients with breast cancer may benefit from treatment with enobosarm, a novel oral selective androgen receptor agonist, according to research presented at ASCO 2021.
“Historically, androgens have been used in the treatment of breast cancer,” Carlo Palmieri, PhD, MBBS, MRCP, of the Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, United Kingdom, said during the presentation. “That fell from use because of their virilizing side effects, as well as the advent of endocrine therapies, which targeted the estrogen receptor.”
However, he noted that recent studies have shown that androgen receptors (ARs) inhibit tumor growth in ER-positive breast cancer.
Palmieri and colleagues conducted a phase 2, open-label, parallel design randomized study of heavily pretreated patients with breast cancer who had AR-positive, ER-positive metastatic breast cancer.
The study comprised 136 women whom investigators randomly assigned 9 mg oral enobosarm daily (n = 72) or 18 mg enobarsarm daily (n = 64).
The researchers used immunohistochemistry to determine AR expression in patient breast cancer samples. They found that tumor objective outcomes correlated with AR expression in percent AR staining.
Using a staining cutoff of 40% AR staining among those with measurable breast cancer, Palmieri and colleagues determined that the clinical benefit rate for a 40% or greater AR staining was 80%, and the rate for less than 40% AR staining was 18% (P < .0001).
They also found that best objective tumor response among patients with 40% or greater AR was 48% and 0% among those with less than 40% AR (P < .0001).
Study data showed that those with 40% or greater AR staining had a median radiographic progression-free survival of 5.47 months and a mean of 7.15 months. For those with less than 40% AR staining, the data showed a median radiographic progression-free survival of 2.72 and a mean of 2.7 months.
Palmieri and colleagues found that the percent AR staining correlation was similar among patients randomly assigned to receive daily 18 mg doses of enobosarm.
“In the previously published data from San Antonio, we showed the efficacy of using enobosarm in heavily pretreated AR-positive, ER-positive, HER2-negative breast cancers,” Palmieri said. “In the current exploratory analysis, looking at various cut-off points, it appears that a cut-off point of 40% or more appears to predict for benefit from enobosarm.”
He added that because of this, the AR “may be used as a biomarker to identify a subset of patients with ER-positive/HER2-negative advanced breast cancer that are more likely to respond to enobosarm.”
Palmieri noted that a phase 3 trial — ARTEST — will assess patients with AR-positive, ER-positive, HER2-negative metastatic breast cancer who were heavily pretreated and had previously progressed on endocrine therapy and CDK4/6 inhibitors who receive enobosarm compared with standard endocrine therapy.
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