title: Everolimus plus exemestane as first-line therapy in HR⁺, HER2⁻ advanced breast cancer in BOLERO-2.
abstract: The present exploratory analysis examined the efficacy, safety, and quality-of-life effects of everolimus (EVE) + exemestane (EXE) in the subgroup of patients in BOLERO-2 whose last treatment before study entry was in the (neo)adjuvant setting. In BOLERO-2, patients with hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2-negative (HER2(-)) advanced breast cancer recurring/progressing after a nonsteroidal aromatase inhibitor (NSAI) were randomly assigned (2:1) to receive EVE (10 mg/day) + EXE (25 mg/day) or placebo (PBO) + EXE. The primary endpoint was progression-free survival (PFS) by local assessment. Overall, 137 patients received first-line EVE + EXE (n = 100) or PBO + EXE (n = 37). Median PFS by local investigator assessment nearly tripled to 11.5 months with EVE + EXE from 4.1 months with PBO + EXE (hazard ratio = 0.39; 95 % CI 0.25-0.62), while maintaining quality of life. This was confirmed by central assessment (15.2 vs 4.2 months; hazard ratio = 0.32; 95 % CI 0.18-0.57). The marked PFS improvement in patients receiving EVE + EXE as first-line therapy for disease recurrence during or after (neo)adjuvant NSAI therapy supports the efficacy of this combination in the first-line setting. Furthermore, the results highlight the potential benefit of early introduction of EVE + EXE in the management of HR(+), HER2(-) advanced breast cancer in postmenopausal patients.
authors.affiliation: Highlands Oncology Group, 3232 N. North Hills Blvd, Fayetteville, AR, 72703, USA, tbeck@hogonc.com.
authors.forename: J Thaddeus
authors.initials: JT
authors.lastname: Beck
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.forename: Fabienne
authors.initials: F
authors.lastname: Lebrun
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: Norikazu
authors.initials: N
authors.lastname: Masuda
authors.forename: Lowell
authors.initials: L
authors.lastname: Hart
authors.forename: Bohuslav
authors.initials: B
authors.lastname: Melichar
authors.forename: Shaker
authors.initials: S
authors.lastname: Dakhil
authors.forename: Matthias
authors.initials: M
authors.lastname: Geberth
authors.forename: Martina
authors.initials: M
authors.lastname: Nunzi
authors.forename: Daniel Y C
authors.initials: DY
authors.lastname: Heng
authors.forename: Thomas
authors.initials: T
authors.lastname: Brechenmacher
authors.forename: Mona
authors.initials: M
authors.lastname: El-Hashimy
authors.forename: Shyanne
authors.initials: S
authors.lastname: Douma
authors.forename: Francois
authors.initials: F
authors.lastname: Ringeisen
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D000068338:Everolimus; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000730:Androstadienes; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000068338:Everolimus; C056516:exemestane; D020123:Sirolimus