title: A network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer.
abstract: The goal of this study was to compare the efficacy and toxicity of chemotherapy to exemestane plus everolimus (EXE/EVE) through a network meta-analysis (NMA) of randomized controlled trials. NMA methods extend standard pairwise meta-analysis to allow simultaneous comparison of multiple treatments while maintaining randomization of individual studies. The method enables "direct" evidence (i.e., evidence from studies directly comparing two interventions) and "indirect" evidence (i.e., evidence from studies that do not compare the two interventions directly) to be pooled under the assumption of evidence consistency. We used NMA to evaluate progression-free survival (PFS) and time to progression (TTP) curves in 34 studies, and response rate (RR) and the hazard ratios (HRs) of the PFS/TTP in 36 studies. A number needed to treat (NNT) analysis was also performed as well as descriptive comparison of reported toxicities. The NMA for PFS/TTP curves and for HR shows EXE/EVE is more efficacious than capecitabine plus sunitinib, CMF, megestrol acetate and tamoxifen, with an average of related-PFS/TTP difference ranging from about 10 months for capecitabine plus sunitinib to more than 6 months for tamoxifen. The NMA for overall RR shows that EXE/EVE provides a better RR than bevacizumab plus capecitabine, capecitabine, capecitabine plus sorafenib, capecitabine plus sunitinib, CMF, gemcitabine plus epirubicin plus paclitaxel, EVE plus tamoxifen, EXE, FEC, megestrol acetate, mitoxantrone, and tamoxifen. Finally, the NMA for NNT shows that EXE/EVE is more beneficial as compared to BMF, capecitabine, capecitabine plus sunitinib, CMF, FEC, megestrol acetate, mitoxantrone, and tamoxifen. The combination of EXE/EVE as first- or second-line therapy for ER+ve/HER2-ve metastatic breast cancer is more efficacious than several chemotherapy regimens that were reported in the literature. Toxicities also favored EXE/EVE in most instances.
authors.affiliation: U.O. di Patologia Mammaria-Breast Cancer Unit, U.S. Terapia Molecolare e Farmacogenomica, AO-Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100, Cremona, Italy. daniele.generali@gmail.com.
authors.forename: Daniele
authors.initials: D
authors.lastname: Generali
authors.affiliation: Centre for Research on Health and Social Care Management (CeRGAS), Bocconi University, Via Roentgen 1, Milan, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Venturini
authors.affiliation: Centre for Research on Health and Social Care Management (CeRGAS), Bocconi University, Via Roentgen 1, Milan, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Rognoni
authors.affiliation: Centre for Research on Health and Social Care Management (CeRGAS), Bocconi University, Via Roentgen 1, Milan, Italy.
authors.forename: Oriana
authors.initials: O
authors.lastname: Ciani
authors.affiliation: Yale Cancer Center, Yale School of Medicine, New Haven, CT, United States.
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
authors.affiliation: Translational Breast Cancer Genomics and Therapeutics Lab, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia.
authors.forename: Sherene
authors.initials: S
authors.lastname: Loi
authors.affiliation: Centre Hospitalier Universitaire du Sart Tilman Liege and Liege University, Liège, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Jerusalem
authors.affiliation: U.O. di Patologia Mammaria-Breast Cancer Unit, U.S. Terapia Molecolare e Farmacogenomica, AO-Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100, Cremona, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bottini
authors.affiliation: Centre for Research on Health and Social Care Management (CeRGAS), Bocconi University, Via Roentgen 1, Milan, Italy.|Department of Policy Analysis and Public Management, Bocconi University, Via Roentgen 1, Milan, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Tarricone
mesh_terms: D000730:Androstadienes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D000068338:Everolimus / Q000008:administration & dosage; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D011960:Receptors, Estrogen / Q000378:metabolism*; D019233:Retreatment; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D000068338:Everolimus; C056516:exemestane