On January 10, 2022, the FDA granted a fast-track designation to enobosarm (Ostarine; Veru), a selective androgen receptor (AR)-targeting agonist, for the treatment of patients with AR-positive, estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer, based on data from the phase 3 ARTEST clinical trial.
The ARTEST study included approximately 210 patients who received oral enobosarm, 9 mg daily. Patients had to have metastatic disease that had progressed after treatment with a nonsteroidal aromatase inhibitor, fulvestrant, and a CDK4/6 inhibitor with an AR nucleus staining of ≥40%. A companion diagnostic test is being developed and validated to identify appropriate patients for this therapy.
Enobosarm was recently assessed as part of the open-label phase 2 G200802 clinical trial in patients with AR-positive, ER-positive metastatic breast cancer. Patients were randomized to 9 mg (N = 72) or 18 mg (N = 64) of oral enobosarm daily. The primary end point of the study was the clinical benefit rate at 6 months, per RECIST version 1.1. The key secondary end points were objective response rate, best overall response, radiographic progression-free survival (PFS), and duration of clinical benefit.
The patients’ median age was 60.8 years in the 9-mg group and 62.1 years in the 18-mg group; 94% of patients in the 9-mg cohort had centrally confirmed AR-positive disease versus 86.5% of patients in the 18-mg cohort.
The clinically meaningful benefit rate was 32% in the 9-mg group compared with 29% in the 18-mg group. By the study end, the median duration of clinical benefit was not reached in the 9-mg group versus 14.1 months in the 18-mg group.
A post-hoc analysis showed that the presence of AR and the amount of expression could predict which patients were most likely to have an antitumor response to enobosarm. The analysis combined patients from the 9-mg and 18-mg groups with a known AR status and measurable disease (N = 84). The 40% AR expression cutoff rate was determined to indicate which patients were most likely to benefit from enobosarm treatment.
At 24 weeks, the clinical benefit rate was 52% at 40% AR staining compared with 14% for <40% staining (P <.0004). Patients had a combined partial and complete response of 34% at 40% AR staining versus 2.7% for those with <40% staining (P <.0003). The median radiographic PFS was 5.47 months for 40% AR staining versus 2.7 months for <40% staining (P <.001).
When using the 40% cutoff, 57% of women with AR-positive, ER-positive, and HER2-negative metastatic breast cancer would qualify for treatment with enobosarm. Women who received 9 mg or 18 mg of enobosarm reported to have an improvement in quality of life, including improved mobility, reduced anxiety or depression, and less pain. A total of 6 patients had drug-related grade 3 or 4 adverse events in the 9-mg group, and 10 patients in the 18-mg group.