@article{c154a3c8c7164f38963273225d97f272,
title = "Everolimus plus exemestane for hormonereceptor- 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.",
keywords = "Everolimus, Exemestane, Hormone-receptor-positive breast cancer, Overall survival",
author = "Martine Piccart and Hortobagyi, {G. N.} and M. Campone and Pritchard, {K. I.} and F. Lebrun and Y. Ito and S. Noguchi and A. Perez and Rugo, {H. S.} and I. Deleu and Burris, {H. A.} and L. Provencher and P. Neven and M. Gnant and M. Shtivelband and C. Wu and J. Fan and W. Feng and T. Taran and J. Baselga",
note = "Funding Information: MP is a board member for PharmaMar; is a consultant to Sanofi, Astellas, Amgen, Bristol-Myers Squibb (BMS), Boehringer Ingelheim, Roche, Synthon, and Bayer; has obtained grant support for her institution from Pfizer, Amgen, Bayer, Boehringer Ingelheim, BMS, GlaxoSmithKline (GSK), Novartis, Roche, and Sanofi; and has received honoraria from Bayer, BMS, Boehringer Ingelheim, Roche, Amgen, Sanofi, and AstraZeneca. GNH has served as a consultant to Antigen Express, Novartis, and Pfizer, and is currently conducting research sponsored by Novartis. MC is a consultant to Novartis and Servier, and has received honoraria from Novartis. KIP has received consulting fees from Sanofi, AstraZeneca, Pfizer, Roche, Amgen, Novartis, GSK, Boehringer Ingelheim, Genomic Health, and Eisai; has received speaker{\textquoteright}s fees from Novartis; and has received travel funding from Novartis, Roche, and AstraZeneca. FL has nothing to disclose. YI has received grant support and honoraria from Chugai, Novartis, Pfizer, Parexel, Boehringer Ingelheim, Daiichi Sankyo, Taiho, and Eisai. SN is an advisor to AstraZeneca and Novartis, and has received grant support and honoraria from AstraZeneca, BMS, Chugai, GSK, Novartis, Pfizer, Sanofi, Taiho, Daiichi Sankyo, and Takeda. AP has nothing to disclose. HSR has received grant support to the regents of the University of California from Pfizer, Novartis, and Merck, and has received travel support from Novartis. ID{\textquoteright}s clinical trial unit receives a yearly grant from Novartis for general purposes. HAB has nothing to disclose. LP has been a member on an Advisory Committee for Roche, Novartis, GSK, and Amgen; has received travel expense reimbursement from Novartis, Roche, and GSK; and has received research grant support from Roche. PN has nothing to disclose. MG has received research support from Sanofi, Novartis, Roche, GSK, Pfizer, and Smith Medical; is a consultant to AstraZeneca, Novartis, and Accelsiors; and has received honoraria (speaking, advisory boards, etc.) and travel support from Amgen, Novartis, GSK, AstraZeneca, Roche, and Nanostring Technologies. MS has nothing to disclose. CW is an employee of Novartis. JF is an employee of Novartis and holds Novartis stock. WF is an employee of Novartis. TT is an employee of Novartis with stock. JB is a consultant for Novartis. Funding Information: This study was sponsored by Novartis Pharmaceuticals Corporation (no grant number). Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation.",
year = "2014",
month = dec,
day = "1",
doi = "10.1093/annonc/mdu456",
language = "English (US)",
volume = "25",
pages = "2357--2362",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "12",
}