title: Comparative efficacy of everolimus plus exemestane versus fulvestrant for hormone-receptor-positive advanced breast cancer following progression/recurrence after endocrine therapy: a network meta-analysis.
abstract: Postmenopausal women with advanced breast cancer recurring/progressing on or after initial (adjuvant or first-line) endocrine therapy may be treated multiple times with one of several endocrine or combinatorial targeted treatment options before initiating chemotherapy. In the absence of direct head-to-head comparisons of these treatment options, an indirect comparison can inform treatment choice. This network meta-analysis compared the efficacy of everolimus plus exemestane with that of fulvestrant 250 and 500 mg in the advanced breast cancer setting following adjuvant or first-line endocrine therapy. The reported hazard ratios (HRs) for progression-free survival (PFS) or time to progression from six studies that formed a network to compare everolimus plus exemestane (BOLERO-2 trial) with fulvestrant were analyzed by means of a Bayesian network meta-analysis. In the primary comparison (PFS analysis based on the local review of disease progression from BOLERO-2 with the data from the other studies), everolimus plus exemestane appeared to be more efficacious than both fulvestrant 250 mg (HR = 0.47; 95 % credible interval [CrI] 0.38-0.58) and 500 mg (HR = 0.59; 95 % CrI 0.45-0.77). Similar results were obtained in an alternate comparison based on central review of disease progression from BOLERO-2 with the data from the other studies (HR = 0.40; 95 % CrI 0.31-0.51 and HR = 0.50; 95 % CrI 0.37-0.67, respectively), and in a subgroup analysis of patients who had received prior aromatase inhibitor therapy (HR = 0.47; 95 % CrI 0.38-0.58 and HR = 0.55; 95 % CrI 0.40-0.76, respectively). These results suggest that everolimus plus exemestane may be more efficacious than fulvestrant in patients with advanced breast cancer who progress on or after adjuvant or first-line therapy with a nonsteroidal aromatase inhibitor.
authors.affiliation: Département de Cancérologie Médicale, Centre Léon Bérard, 28 rue Laënnec, 69008, Lyon Cedex 08, France, thomas.bachelot@lyon.unicancer.fr.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.forename: Rachael
authors.initials: R
authors.lastname: McCool
authors.forename: Steven
authors.initials: S
authors.lastname: Duffy
authors.forename: Julie
authors.initials: J
authors.lastname: Glanville
authors.forename: Danielle
authors.initials: D
authors.lastname: Varley
authors.forename: Kelly
authors.initials: K
authors.lastname: Fleetwood
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Guy
authors.initials: G
authors.lastname: Jerusalem
mesh_terms: D000730:Androstadienes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002986:Clinical Trials as Topic; D018450:Disease Progression; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068338:Everolimus; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; D004958:Estradiol; D000068338:Everolimus; D000077267:Fulvestrant; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D020123:Sirolimus; C056516:exemestane