title: Health-related quality of life of patients with advanced breast cancer treated with everolimus plus exemestane versus placebo plus exemestane in the phase 3, randomized, controlled, BOLERO-2 trial.
abstract: BACKGROUND
  The randomized, controlled BOLERO-2 (Breast Cancer Trials of Oral Everolimus) trial demonstrated significantly improved progression-free survival with the use of everolimus plus exemestane (EVE + EXE) versus placebo plus exemestane (PBO + EXE) in patients with advanced breast cancer who developed disease progression after treatment with nonsteroidal aromatase inhibitors. This analysis investigated the treatment effects on health-related quality of life (HRQOL).
  
  
  METHODS
  Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questionnaire, HRQOL was assessed at baseline and every 6 weeks thereafter until disease progression and/or treatment discontinuation. The 30 items in 15 subscales of the QLQ-C30 include global health status wherein higher scores (range, 0-100) indicate better HRQOL. This analysis included a protocol-specified time to definitive deterioration (TDD) analysis at a 5% decrease in HRQOL versus baseline, with no subsequent increase above this threshold. The authors report additional sensitivity analyses using 10-point minimal important difference decreases in the global health status score versus baseline. Treatment arms were compared using the stratified log-rank test and Cox proportional hazards model adjusted for trial stratum (visceral metastases, previous hormone sensitivity), age, sex, race, baseline global health status score and Eastern Cooperative Oncology Group performance status, prognostic risk factors, and treatment history.
  
  
  RESULTS
  Baseline global health status scores were found to be similar between treatment groups (64.7 vs 65.3). The median TDD in HRQOL was 8.3 months with EVE + EXE versus 5.8 months with PBO + EXE (hazard ratio, 0.74; P = .0084). At the 10-point minimal important difference, the median TDD with EVE + EXE was 11.7 months versus 8.4 months with PBO + EXE (hazard ratio, 0.80; P = .1017).
  
  
  CONCLUSIONS
  In patients with advanced breast cancer who develop disease progression after treatment with nonsteroidal aromatase inhibitors, EVE + EXE was associated with a longer TDD in global HRQOL versus PBO + EXE.
authors.affiliation: Drug Development Program, Sarah Cannon Research Institute, Nashville, Tennessee, USA. howard.burris@scresearch.net
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
authors.forename: Fabienne
authors.initials: F
authors.lastname: Lebrun
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.forename: J Thaddeus
authors.initials: JT
authors.lastname: Beck
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart
authors.forename: Patrick
authors.initials: P
authors.lastname: Neven
authors.forename: Jose
authors.initials: J
authors.lastname: Baselga
authors.forename: Katarina
authors.initials: K
authors.lastname: Petrakova
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Anna
authors.initials: A
authors.lastname: Komorowski
authors.forename: Edmond
authors.initials: E
authors.lastname: Chouinard
authors.forename: Robyn
authors.initials: R
authors.lastname: Young
authors.forename: Michael
authors.initials: M
authors.lastname: Gnant
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.forename: Lee
authors.initials: L
authors.lastname: Bennett
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Ricci
authors.forename: Hounayda
authors.initials: H
authors.lastname: Bauly
authors.forename: Tetiana
authors.initials: T
authors.lastname: Taran
authors.forename: Tarek
authors.initials: T
authors.lastname: Sahmoud
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
mesh_terms: D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000068338:Everolimus; D005260:Female; D006304:Health Status; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D017698:Postmenopause; D016016:Proportional Hazards Models; D011788:Quality of Life; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; D000068338:Everolimus; C056516:exemestane; D020123:Sirolimus