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Activity and safety of enobosarm, a novel, oral, selective androgen receptor modulator, in androgen receptor-positive, oestrogen receptor-positive, and HER2-negative advanced breast cancer (study G200802): a randomised, open-label, multicentre, multinational, parallel design, phase 2 trial

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posted on 2024-03-25, 14:48 authored by Carlo Palmieri, Hannah Linden, Stephen N Birrell, Sally WheelwrightSally Wheelwright, Elgene Lim, Lee S Schwartzberg, Amy R Dwyer, Theresa E Hickey, Hope S Rugo, Patrick Cobb, et al.

Background

The androgen receptor is a tumour suppressor in oestrogen receptor-positive breast cancer. The activity and safety of enobosarm, an oral selective androgen receptor modulator, was evaluated in women with oestrogen receptor (ER)-positive, HER2-negative, and androgen receptor (AR)-positive disease.

Methods

Women who were postmenopausal (aged ≥18 years) with previously treated ER-positive, HER2-negative, locally advanced or metastatic breast cancer with an Eastern Cooperative Oncology Group performance status of 0–2 were enrolled in a randomised, open-label, multicentre, multinational, parallel design, phase 2 trial done at 35 cancer treatment centres in nine countries. Participants were stratified on the setting of immediately preceding endocrine therapy and the presence of bone-only metastasis and randomly assigned (1:1) to 9 mg or 18 mg oral enobosarm daily using an interactive web response system. The primary endpoint was clinical benefit rate at 24 weeks in those with centrally confirmed AR-positive disease (ie, the evaluable population). This trial is registered with ClinicalTrials.gov (NCT02463032).

Findings

Between Sept 10, 2015, and Nov 28, 2017, 136 (79%) of 172 patients deemed eligible were randomly assigned to 9 mg (n=72) or 18 mg (n=64) oral enobosarm daily. Of these 136 patients, 102 (75%) patients formed the evaluable population (9 mg, n=50; 18 mg, n=52). The median age was 60·5 years (IQR 52·3–69·3) in the 9 mg group and 62·5 years (54·0–69·3) in the 18 mg group. The median follow-up was 7·5 months (IQR 2·9–14·1). At 24 weeks, 16 (32%, 95% CI 20–47) of 50 in the 9 mg group and 15 (29%, 17–43) of 52 in the 18 mg group had clinical benefit. Six (8%) of 75 patients who received 9 mg and ten (16%) of 61 patients who received 18 mg had grade 3 or grade 4 drug-related adverse events, most frequently increased hepatic transaminases (three [4%] of 75 in the 9 mg group and two [3%] of 61 in the 18 mg group), hypercalcaemia (two [3%] and two [3%]), and fatigue (one [1%] and two [3%]). Four deaths (one in the 9 mg group and three in the 18 mg group) were deemed unrelated to the study drug.

Interpretation

Enobosarm has anti-tumour 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.

History

Publication status

  • Published

File Version

  • Published version

Journal

The Lancet Oncology

ISSN

1213-9432

Publisher

Elsevier

Issue

3

Volume

25

Page range

317-325

Department affiliated with

  • Sussex Health Outcomes Research & Education in Cancer (SHORE-C) Publications
  • BSMS Publications

Institution

University of Sussex

Full text available

  • Yes

Peer reviewed?

  • Yes

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