title: 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.
  
  
  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.
  
  
  BACKGROUND
  NCT00863655.
authors.affiliation: Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: martine.piccart@bordet.be.
authors.forename: M
authors.initials: M
authors.lastname: Piccart
authors.affiliation: Department of Breast Medical Oncology, Multidisciplinary Breast Cancer Research Program, University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: G N
authors.initials: GN
authors.lastname: Hortobagyi
authors.affiliation: Institut de Cancérologie de l'Ouest, René Gauducheau, Centre de Recherche en Cancérologie, Nantes Saint Herblain, France.
authors.forename: M
authors.initials: M
authors.lastname: Campone
authors.affiliation: Department of Medicine, Sunnybrook Odette Cancer Centre and the University of Toronto, Toronto, Canada.
authors.forename: K I
authors.initials: KI
authors.lastname: Pritchard
authors.affiliation: Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Lebrun
authors.affiliation: Department of Breast Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo.
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Noguchi
authors.affiliation: Breast Cancer Centers, Memorial Cancer Institute, Hollywood.
authors.forename: A
authors.initials: A
authors.lastname: Perez
authors.affiliation: Breast Oncology and Clinical Trials Education, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, USA.
authors.forename: H S
authors.initials: HS
authors.lastname: Rugo
authors.affiliation: Oncologic Centre, AZ Nikolaas, Sint-Niklaas, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Deleu
authors.affiliation: Sarah Cannon Research Institute, Nashville, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Burris
authors.affiliation: Centre des Maladies du Sein Deschênes-Fabia, CHU-Hôpital du Saint Sacrement, Québec, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Provencher
authors.affiliation: Multidisciplinary Breast Centre and Department of Gynecologic Oncology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Neven
authors.affiliation: Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Gnant
authors.affiliation: Ironwood Cancer & Research Centers, Chandler.
authors.forename: M
authors.initials: M
authors.lastname: Shtivelband
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover.
authors.forename: C
authors.initials: C
authors.lastname: Wu
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover.
authors.forename: J
authors.initials: J
authors.lastname: Fan
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover.
authors.forename: W
authors.initials: W
authors.lastname: Feng
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover.
authors.forename: T
authors.initials: T
authors.lastname: Taran
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, USA.
authors.forename: J
authors.initials: J
authors.lastname: Baselga
mesh_terms: D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms; D004311:Double-Blind Method; D066246:ErbB Receptors / Q000378:metabolism; D000068338:Everolimus; D005260:Female; D006801:Humans; D010919:Placebos; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016019:Survival Analysis
chemical_list: D000730:Androstadienes; D010919:Placebos; D000068338:Everolimus; D066246:ErbB Receptors; C056516:exemestane; D020123:Sirolimus
keywords: everolimus; exemestane; hormone-receptor-positive breast cancer; overall survival