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.


Palmieri, Carlo ORCID: 0000-0001-9496-2718, Linden, Hannah, Birrell, Stephen N, Wheelwright, Sally ORCID: 0000-0003-0657-2483, Lim, Elgene, Schwartzberg, Lee S, Dwyer, Amy R, Hickey, Theresa E, Rugo, Hope S, Cobb, Patrick et al (show 5 more authors) (2024) 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. The Lancet. Oncology, 25 (3). pp. 317-325. ISSN 1470-2045, 1474-5488

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Abstract

<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>GTx.

Item Type: Article
Uncontrolled Keywords: Humans, Breast Neoplasms, Anilides, Receptor, erbB-2, Receptors, Androgen, Receptors, Estrogen, Antineoplastic Combined Chemotherapy Protocols, Aged, Middle Aged, Female
Depositing User: Symplectic Admin
Date Deposited: 20 Aug 2024 09:57
Last Modified: 07 Dec 2024 23:43
DOI: 10.1016/s1470-2045(24)00004-4
Open Access URL: https://doi.org/10.1016/S1470-2045(24)00004-4
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3183906
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