title: Health-related quality of life and disease symptoms in postmenopausal women with HR(+), HER2(-) advanced breast cancer treated with everolimus plus exemestane versus exemestane monotherapy.
abstract: OBJECTIVE
  Everolimus (EVE)+exemestane (EXE; n = 485) more than doubled median progression-free survival versus placebo (PBO) + EXE (n = 239), with a manageable safety profile and no deterioration in health-related quality-of-life (HRQOL) in patients with hormone-receptor-positive (HR(+)) advanced breast cancer (ABC) who recurred or progressed on/after nonsteroidal aromatase inhibitor (NSAI) therapy. To further evaluate EVE + EXE impact on disease burden, we conducted additional post-hoc analyses of patient-reported HRQOL.
  
  
  METHODS
  HRQOL was assessed using EORTC QLQ-C30 and QLQ-BR23 questionnaires at baseline and every 6 weeks thereafter until treatment discontinuation because of disease progression, toxicity, or consent withdrawal. Endpoints included the QLQ-C30 Global Health Status (QL2) scale, the QLQ-BR23 breast symptom (BRBS), and arm symptom (BRAS) scales. Between-group differences in change from baseline were assessed using linear mixed models with selected covariates. Sensitivity analysis using pattern-mixture models determined the effect of study discontinuation on/before week 24. Treatment arms were compared using differences of least squares mean (LSM) changes from baseline and 95% confidence intervals (CIs) at each timepoint and overall.
  
  
  BACKGROUND
  Clinicaltrials.gov: NCT00863655.
  
  
  METHODS
  Progression-free survival, survival, response rate, safety, and HRQOL.
  
  
  RESULTS
  Linear mixed models (primary model) demonstrated no statistically significant overall difference between EVE + EXE and PBO + EXE for QL2 (LSM difference = -1.91; 95% CI = -4.61, 0.78), BRBS (LSM difference = -0.18; 95% CI = -1.98, 1.62), or BRAS (LSM difference = -0.42; 95% CI = -2.94, 2.10). Based on pattern-mixture models, patients who dropped out early had worse QL2 decline on both treatments. In the expanded pattern-mixture model, EVE + EXE-treated patients who did not drop out early had stable BRBS and BRAS relative to PBO + EXE.
  
  
  CONCLUSIONS
  HRQOL data were not collected after disease progression.
  
  
  CONCLUSIONS
  These analyses confirm that EVE + EXE provides clinical benefit without adversely impacting HRQOL in patients with HR(+) ABC who recurred/progressed on prior NSAIs versus endocrine therapy alone.
authors: Institut de Cancérologie de l'Ouest - Centre Rene Gauducheau , Saint Herblain , France.
authors: Mario
authors: M
authors: Campone
authors: J Thaddeus
authors: JT
authors: Beck
authors: Michael
authors: M
authors: Gnant
authors: Patrick
authors: P
authors: Neven
authors: Kathleen I
authors: KI
authors: Pritchard
authors: Thomas
authors: T
authors: Bachelot
authors: Louise
authors: L
authors: Provencher
authors: Hope S
authors: HS
authors: Rugo
authors: Martine
authors: M
authors: Piccart
authors: Gabriel N
authors: GN
authors: Hortobagyi
authors: Martina
authors: M
authors: Nunzi
authors: Daniel Y C
authors: DY
authors: Heng
authors: José
authors: J
authors: Baselga
authors: Anna
authors: A
authors: Komorowski
authors: Shinzaburo
authors: S
authors: Noguchi
authors: Jun
authors: J
authors: Horiguchi
authors: Lee
authors: L
authors: Bennett
authors: Ryan
authors: R
authors: Ziemiecki
authors: Jie
authors: J
authors: Zhang
authors: Ayelet
authors: A
authors: Cahana
authors: Tetiana
authors: T
authors: Taran
authors: Tarek
authors: T
authors: Sahmoud
authors: Howard A
authors: HA
authors: Burris
mesh_terms: D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018450:Disease Progression; D018572:Disease-Free Survival; D000068338:Everolimus; D005260:Female; D006304:Health Status; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008875:Middle Aged; D010919:Placebos / Q000627:therapeutic use; D011788:Quality of Life; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D000068338:Everolimus; D007166:Immunosuppressive Agents; D010919:Placebos; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D020123:Sirolimus; C508053:ERBB2 protein, human; C056516:exemestane