title: Effect of visceral metastases on the efficacy and safety of everolimus in postmenopausal women with advanced breast cancer: subgroup analysis from the BOLERO-2 study.
abstract: BACKGROUND
  Everolimus (EVE; an inhibitor of mammalian target of rapamycin [mTOR]) enhances treatment options for postmenopausal women with hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2-negative (HER2(-)) advanced breast cancer (ABC) who progress on a non-steroidal aromatase inhibitor (NSAI). This is especially true for patients with visceral disease, which is associated with poor prognosis. The BOLERO-2 (Breast cancer trial of OraLEveROlimus-2) trial showed that combination treatment with EVE and exemestane (EXE) versus placebo (PBO)+EXE prolonged progression-free survival (PFS) by both investigator (7.8 versus 3.2 months, respectively) and independent (11.0 versus 4.1 months, respectively) central assessment in postmenopausal women with HR(+), HER2(-) ABC recurring/progressing during/after NSAI therapy. The BOLERO-2 trial included a substantial proportion of patients with visceral metastases (56%).
  
  
  METHODS
  Prespecified exploratory subgroup analysis conducted to evaluate the efficacy and safety of EVE+EXE versus PBO+EXE in a prospectively defined subgroup of patients with visceral metastases.
  
  
  RESULTS
  At a median follow-up of 18 months, EVE+EXE significantly prolonged median PFS compared with PBO+EXE both in patients with visceral metastases (N=406; 6.8 versus 2.8 months) and in those without visceral metastases (N=318; 9.9 versus 4.2 months). Improvements in PFS with EVE+EXE versus PBO+EXE were also observed in patients with visceral metastases regardless of Eastern Cooperative Oncology Group performance status (ECOG PS). Patients with visceral metastases and ECOG PS 0 had a median PFS of 6.8 months with EVE+EXE versus 2.8 months with PBO+EXE. Among patients with visceral metastases and ECOG PS ≥1, EVE+EXE treatment more than tripled median PFS compared with PBO+EXE (6.8 versus 1.5 months).
  
  
  CONCLUSIONS
  Adding EVE to EXE markedly extended PFS by ≥4 months among patients with HR(+) HER2(-) ABC regardless of the presence of visceral metastases.
authors.affiliation: Institut de Cancérologie de l'Ouest-René Gauducheau, Centre de Recherche en Cancérologie, Boulevard Jacques Monod, 44805 Saint Herblain-Nantes cedex, France. Mario.Campone@ico.unicancer.fr
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.forename: Michael
authors.initials: M
authors.lastname: Gnant
authors.forename: Ines
authors.initials: I
authors.lastname: Deleu
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.forename: Barbara
authors.initials: B
authors.lastname: Pistilli
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
authors.forename: Mikhail
authors.initials: M
authors.lastname: Shtivelband
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.forename: Louise
authors.initials: L
authors.lastname: Provencher
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
authors.forename: Lowell
authors.initials: L
authors.lastname: Hart
authors.forename: Bohuslav
authors.initials: B
authors.lastname: Melichar
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Francis
authors.initials: F
authors.lastname: Arena
authors.forename: José
authors.initials: J
authors.lastname: Baselga
authors.forename: Ashok
authors.initials: A
authors.lastname: Panneerselvam
authors.forename: Aurelia
authors.initials: A
authors.lastname: Héniquez
authors.forename: Mona
authors.initials: M
authors.lastname: El-Hashimyt
authors.forename: Tetiana
authors.initials: T
authors.lastname: Taran
authors.forename: Tarek
authors.initials: T
authors.lastname: Sahmoud
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart
mesh_terms: D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017326:Clinical Trials, Phase III as Topic; D000068338:Everolimus; D005076:Exanthema / Q000139:chemically induced; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009362:Neoplasm Metastasis; D010919:Placebos; D017698:Postmenopause; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D013280:Stomatitis / Q000139:chemically induced; D016896:Treatment Outcome; D014781:Viscera / Q000473:pathology
chemical_list: D000730:Androstadienes; D000068338:Everolimus; D010919:Placebos; D018719:Erb-b2 Receptor Tyrosine Kinases; D011987:Receptors, Steroid; D020123:Sirolimus; C056516:exemestane
keywords: Advanced breast cancer; Everolimus; Exemestane; Visceral metastases