title: Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis.
abstract: BACKGROUND
  Effective treatments for hormone-receptor-positive (HR(+)) breast cancer (BC) following relapse/progression on nonsteroidal aromatase inhibitor (NSAI) therapy are needed. Initial Breast Cancer Trials of OraL EveROlimus-2 (BOLERO-2) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival (PFS) versus placebo plus exemestane alone in this patient population.
  
  
  METHODS
  BOLERO-2 is a phase 3, double-blind, randomized, international trial comparing everolimus (10 mg/day) plus exemestane (25 mg/day) versus placebo plus exemestane in postmenopausal women with HR(+) advanced BC with recurrence/progression during or after NSAIs. The primary endpoint was PFS by local investigator review, and was confirmed by independent central radiology review. Overall survival, response rate, and clinical benefit rate were secondary endpoints.
  
  
  RESULTS
  Final study results with median 18-month follow-up show that median PFS remained significantly longer with everolimus plus exemestane versus placebo plus exemestane [investigator review: 7.8 versus 3.2 months, respectively; hazard ratio = 0.45 (95% confidence interval 0.38-0.54); log-rank P < 0.0001; central review: 11.0 versus 4.1 months, respectively; hazard ratio = 0.38 (95% confidence interval 0.31-0.48); log-rank P < 0.0001] in the overall population and in all prospectively defined subgroups, including patients with visceral metastases, [corrected] and irrespective of age. The incidence and severity of adverse events were consistent with those reported at the interim analysis and in other everolimus trials.
  
  
  CONCLUSIONS
  The addition of everolimus to exemestane markedly prolonged PFS in patients with HR(+) advanced BC with disease recurrence/progression following prior NSAIs. These results further support the use of everolimus plus exemestane in this patient population. ClinicalTrials.gov #NCT00863655.
authors.affiliation: Sarah Cannon Research Institute and Tennessee Oncology, PLLC, Nashville, TN, 37203, USA, dyardley@tnonc.com.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
authors.forename: José
authors.initials: J
authors.lastname: Baselga
authors.forename: Michael
authors.initials: M
authors.lastname: Gnant
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.forename: Barbara
authors.initials: B
authors.lastname: Pistilli
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart
authors.forename: Bohuslav
authors.initials: B
authors.lastname: Melichar
authors.forename: Katarina
authors.initials: K
authors.lastname: Petrakova
authors.forename: Francis P
authors.initials: FP
authors.lastname: Arena
authors.forename: Frans
authors.initials: F
authors.lastname: Erdkamp
authors.forename: Wael A
authors.initials: WA
authors.lastname: Harb
authors.forename: Wentao
authors.initials: W
authors.lastname: Feng
authors.forename: Ayelet
authors.initials: A
authors.lastname: Cahana
authors.forename: Tetiana
authors.initials: T
authors.lastname: Taran
authors.forename: David
authors.initials: D
authors.lastname: Lebwohl
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D004311:Double-Blind Method; D000068338:Everolimus; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008875:Middle Aged; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000068338:Everolimus; C056516:exemestane; D020123:Sirolimus