title: Safety and efficacy of everolimus with exemestane vs. exemestane alone in elderly patients with HER2-negative, hormone receptor-positive breast cancer in BOLERO-2.
abstract: BACKGROUND
  Postmenopausal women with hormone receptor-positive (HR(+)) breast cancer in whom disease progresses or there is recurrence while taking a nonsteroidal aromatase inhibitor (NSAI) are usually treated with exemestane (EXE), but no single standard of care exists in this setting. The BOLERO-2 trial demonstrated that adding everolimus (EVE) to EXE improved progression-free survival (PFS) while maintaining quality of life when compared with EXE alone. Because many women with HR(+) advanced breast cancer are elderly, the tolerability profile of EVE plus EXE in this population is of interest.
  
  
  METHODS
  BOLERO-2, a phase III randomized trial, compared EVE (10 mg/d) and placebo (PBO), both plus EXE (25 mg/d), in 724 postmenopausal women with HR(+) advanced breast cancer recurring/progressing after treatment with NSAIs. Safety and efficacy data in elderly patients are reported at 18-month median follow-up.
  
  
  RESULTS
  Baseline disease characteristics and treatment histories among the elderly subsets (≥ 65 years, n = 275; ≥ 70 years, n = 164) were generally comparable with younger patients. The addition of EVE to EXE improved PFS regardless of age (hazard ratio, 0.59 [≥ 65 years] and 0.45 [≥ 70 years]). Adverse events (AEs) of special interest (all grades) that occurred more frequently with EVE than with PBO included stomatitis, infections, rash, pneumonitis, and hyperglycemia. Elderly EVE-treated patients had similar incidences of these AEs as did younger patients but had more on-treatment deaths.
  
  
  CONCLUSIONS
  Adding EVE to EXE offers substantially improved PFS over EXE and was generally well tolerated in elderly patients with HR(+) advanced breast cancer. Careful monitoring and appropriate dose reductions or interruptions for AE management are recommended during treatment with EVE in this patient population.
authors.affiliation: Sunnybrook Odette Cancer Centre and the University of Toronto, Toronto, Ontario, Canada. Electronic address: Kathy.pritchard@sunnybrook.ca.
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.forename: Shaker
authors.initials: S
authors.lastname: Dakhil
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.forename: Tibor
authors.initials: T
authors.lastname: Csöszi
authors.forename: José
authors.initials: J
authors.lastname: Baselga
authors.forename: Puttisak
authors.initials: P
authors.lastname: Puttawibul
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart
authors.forename: Daniel
authors.initials: D
authors.lastname: Heng
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
authors.forename: Vichien
authors.initials: V
authors.lastname: Srimuninnimit
authors.forename: Hugues
authors.initials: H
authors.lastname: Bourgeois
authors.forename: Antonio
authors.initials: A
authors.lastname: Gonzalez Martin
authors.forename: Karen
authors.initials: K
authors.lastname: Osborne
authors.forename: Ashok
authors.initials: A
authors.lastname: Panneerselvam
authors.forename: Tetiana
authors.initials: T
authors.lastname: Taran
authors.forename: Tarek
authors.initials: T
authors.lastname: Sahmoud
authors.forename: Michael
authors.initials: M
authors.lastname: Gnant
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007390:International Agencies; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012449:Safety; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D015996:Survival Rate
chemical_list: D000730:Androstadienes; D000068338:Everolimus; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D020123:Sirolimus; C508053:ERBB2 protein, human; C056516:exemestane
keywords: Advanced breast cancer; Endocrine resistance; Geriatric; Progression-free survival; Safety