Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2†.

Abstract

BACKGROUND:

The BOLERO-2 study previously demonstrated that adding everolimus (EVE) to exemestane (EXE) significantly improved progression-free survival (PFS) by more than twofold in patients with hormone-receptor-positive (HR(+)), HER2-negative advanced breast cancer that recurred or progressed during/after treatment with nonsteroidal aromatase inhibitors (NSAIs). The overall survival (OS) analysis is presented here.

PATIENTS AND METHODS:

BOLERO-2 is a phase III, double-blind, randomized international trial comparing EVE 10 mg/day plus EXE 25 mg/day versus placebo (PBO) + EXE 25 mg/day in postmenopausal women with HR(+) advanced breast cancer with prior exposure to NSAIs. The primary end point was PFS by local investigator assessment; OS was a key secondary end point.

RESULTS:

At the time of data cutoff (3 October 2013), 410 deaths had occurred and 13 patients remained on treatment. Median OS in patients receiving EVE + EXE was 31.0 months [95% confidence interval (CI) 28.0-34.6 months] compared with 26.6 months (95% CI 22.6-33.1 months) in patients receiving PBO + EXE (hazard ratio = 0.89; 95% CI 0.73-1.10; log-rank P = 0.14). Poststudy treatments were received by 84% of patients in the EVE + EXE arm versus 90% of patients in the PBO + EXE arm. Types of poststudy therapies were balanced across arms, except for chemotherapy (53% EVE + EXE versus 63% PBO + EXE). No new safety concerns were identified.

CONCLUSIONS:

In BOLERO-2, adding EVE to EXE did not confer a statistically significant improvement in the secondary end point OS despite producing a clinically meaningful and statistically significant improvement in the primary end point, PFS (4.6-months prolongation in median PFS; P < 0.0001). Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting.

TRIAL REGISTRATION NUMBER:

NCT00863655.

• Authors: M Piccart, G N Hortobagyi, M Campone, K I Pritchard, F Lebrun, Y Ito, S Noguchi, A Perez, H S Rugo, I Deleu, H A Burris 3rd, L Provencher, P Neven, M Gnant, M Shtivelband, C Wu, J Fan, W Feng, T Taran, J Baselga
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 25 Issue 12 Pg. 2357-2362 (Dec 2014) ISSN: 1569-8041 [Electronic] England
• PMID: 25231953 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Androstadienes
• Placebos
• Everolimus
• ErbB Receptors
• exemestane
• Sirolimus

Topics

• Androstadienes (adverse effects, therapeutic use)
• Breast Neoplasms
• Double-Blind Method
• ErbB Receptors (metabolism)
• Everolimus
• Female
• Humans
• Placebos
• Sirolimus (adverse effects, analogs & derivatives, therapeutic use)
• Survival Analysis