Differential benefit of adjuvant everolimus according to endocrine therapy backbone in the randomized UNIRAD trial.

Saint-Ghislain, M; Chabaud, S; Dalenc, F; Allouache, D; Cameron, D; Martinez, M; Grenier, J; Barthelemy, P; Brunt, M; Kaluzinski, L; Mailliez, A; Legouffe, E; Hardy-Bessard, A-C; Giacchetti, S; Mouret-Reynier, M-A; Canon, J-L; Bliss, J; Lemonnier, J; Andre, F; Bachelot, T; Cottu, P

Abstract

The randomized, double-blind UNIRAD trial evaluating the addition of 2 years of everolimus to endocrine therapy in patients with high-risk, early luminal breast cancer failed to demonstrate a benefit. We report the subgroup analyses. We randomly assigned 1278 patients in a 1 : 1 ratio to receive 2 years of placebo or everolimus, added to endocrine therapy for up to 4 years after initiation. Randomization was stratified by endocrine therapy agent, prior adjuvant versus neoadjuvant therapy, progesterone receptor expression, and lymph node involvement. Subgroup analyses by each stratification factor were pre-specified. Post hoc analyses were carried out according to menopausal status and age. Treatment adherence was also analyzed. We observed a limited trend toward more favorable prognostic features in tamoxifen-treated patients, with more frequent estrogen receptor-positive/progesterone receptor-positive tumors (88.5% versus 84.1%, P = 0.026) and less frequent pN2-positive status (39.8% versus 46.0%, P = 0.032). In premenopausal women, we observed a numerical benefit of everolimus: 3-year disease-free survival was 86% in the placebo group and 90% in the everolimus group (hazard ratio 0.76, 95% confidence interval 0.43-1.34). In premenopausal patients treated with tamoxifen (n = 153; 12.3%), we observed an even stronger trend in favor of everolimus as 3-year DFS was 84% in the placebo group and 91% in the everolimus group (hazard ratio 0.54, 95% confidence interval 0.28-1.02). Early discontinuation of either everolimus or placebo was less frequent in the tamoxifen group than in the aromatase inhibitor group: 48.0% versus 56.9% (P = 0.028). The present post hoc analyses generate hypotheses regarding the interaction between menopausal status, tamoxifen, and everolimus in patients with high-risk, ER-positive, human epidermal growth factor receptor type 2-negative early breast cancer. They suggest that tamoxifen alone is an underpowered endocrine treatment in high-risk premenopausal patients. [Abstract copyright: Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.]

Citation

Saint-Ghislain, M., Chabaud, S., Dalenc, F., Allouache, D., Cameron, D., Martinez, M., Grenier, J., Barthelemy, P., Brunt, M., Kaluzinski, L., Mailliez, A., Legouffe, E., Hardy-Bessard, A.-C., Giacchetti, S., Mouret-Reynier, M.-A., Canon, J.-L., Bliss, J., Lemonnier, J., Andre, F., Bachelot, T., & Cottu, P. (2025). Differential benefit of adjuvant everolimus according to endocrine therapy backbone in the randomized UNIRAD trial. ESMO Open, 10(5), Article 105050. https://doi.org/10.1016/j.esmoop.2025.105050

• Journal Article Type: Article
• Acceptance Date: Apr 15, 2025
• Online Publication Date: Apr 15, 2025
• Publication Date: Apr 15, 2025
• Deposit Date: May 7, 2025
• Journal: ESMO open
• Print ISSN: 2059-7029
• Electronic ISSN: 2059-7029
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 5
• Article Number: 105050
• DOI: https://doi.org/10.1016/j.esmoop.2025.105050
• Keywords: luminal breast cancer, everolimus, adjuvant therapy, premenopausal
• Public URL: https://keele-repository.worktribe.com/output/1230592