title: Selecting first-line bevacizumab-containing therapy for advanced breast cancer: TURANDOT risk factor analyses.
abstract: BACKGROUND
  The randomised phase III TURANDOT trial compared first-line bevacizumab-paclitaxel (BEV-PAC) vs bevacizumab-capecitabine (BEV-CAP) in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). The interim analysis revealed no difference in overall survival (OS; primary end point) between treatment arms; however, progression-free survival (PFS) and objective response rate were significantly superior with BEV-PAC. We sought to identify patient populations that may be most appropriately treated with one or other regimen.
  
  
  METHODS
  Patients with HER2-negative LR/mBC who had received no prior chemotherapy for advanced disease were randomised to either BEV-PAC (bevacizumab 10 mg kg(-1) days 1 and 15 plus paclitaxel 90 mg m(-2) days 1, 8 and 15 q4w) or BEV-CAP (bevacizumab 15 mg kg(-1) day 1 plus capecitabine 1000 mg m(-2) bid days 1-14 q3w). The study population was categorised into three cohorts: triple-negative breast cancer (TNBC), high-risk hormone receptor-positive (HR+) and low-risk HR+. High- and low-risk HR+ were defined, respectively, as having ⩾2 vs ⩽1 of the following four risk factors: disease-free interval ⩽24 months; visceral metastases; prior (neo)adjuvant anthracycline and/or taxane; and metastases in ⩾3 organs.
  
  
  RESULTS
  The treatment effect on OS differed between cohorts. Non-significant OS trends favoured BEV-PAC in the TNBC cohort and BEV-CAP in the low-risk HR+ cohort. In all three cohorts, there was a non-significant PFS trend favouring BEV-PAC. Grade ⩾3 adverse events were consistently less common with BEV-CAP.
  
  
  CONCLUSIONS
  A simple risk factor index may help in selecting bevacizumab-containing regimens, balancing outcome, safety profile and patient preference. Final OS results are expected in 2015 (ClinicalTrials.gov NCT00600340).
authors.affiliation: Clinical Division of Oncology and Department of Medicine I, Medical University of Vienna and CECOG, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Brodowicz
authors.affiliation: Ráth György u. 7-9, National Institute of Oncology, H-1122 Budapest, Hungary.
authors.forename: I
authors.initials: I
authors.lastname: Lang
authors.affiliation: Department of Oncotherapy, University of Szeged, H-6720 Szeged, Korányi fasor 12, H-6720 Szeged, Hungary.
authors.forename: Z
authors.initials: Z
authors.lastname: Kahan
authors.affiliation: IIIrd Medical Department, Paracelsus Medical University Hospital Salzburg and AGMT, Salzburg, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Greil
authors.affiliation: Institute of Oncology, Clinical Center, University of Sarajevo, Bolnicka 27, 71000 Sarajevo, Bosnia and Herzegovina.
authors.forename: S
authors.initials: S
authors.lastname: Beslija
authors.affiliation: Davidoff Center, Rabin Medical Center, Kaplan Street, Petah Tiqwa 49100, Israel.
authors.forename: S M
authors.initials: SM
authors.lastname: Stemmer
authors.affiliation: Breast Oncology Institute, Sheba Medical Center, 52621 Tel Hashomer, Ramat-Gan, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Kaufman
authors.affiliation: Department of Oncology, First Faculty of Medicine and General Teaching Hospital, Charles University Prague, U Nemocnice 2, 128 08 Prague 2, Czech Republic.
authors.forename: L
authors.initials: L
authors.lastname: Petruzelka
authors.affiliation: Department of Breast Tumors, Cancer Institute Ion Chiricuţă, Republicii 34-36, 400015 Cluj-Napoca, Romania.
authors.forename: A
authors.initials: A
authors.lastname: Eniu
authors.affiliation: University of Medicine and Pharmacy Bucharest, Soseaua Fundeni, Nr 252, Sector 2, Bucharest 022328, Romania.
authors.forename: R
authors.initials: R
authors.lastname: Anghel
authors.affiliation: Department of Medical Oncology, Hospital Serdika, 6 Damyan Gruev street, 1303 Sofia, Bulgaria.
authors.forename: K
authors.initials: K
authors.lastname: Koynov
authors.affiliation: Department of Medical Oncology, University Hospital Zagreb-Rebro, Medical University of Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia.
authors.forename: D
authors.initials: D
authors.lastname: Vrbanec
authors.affiliation: Oncology Department, European Health Centre Otwock, ul. Borowa 14/18, 04-500 Otwock, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Pienkowski
authors.affiliation: Department of Oncology, Palacký University Medical School, I. P. Pavlova 6, 775 20 Olomouc, Czech Republic.
authors.forename: B
authors.initials: B
authors.lastname: Melichar
authors.affiliation: St Elisabeth Cancer Institute, Heydukova 10, 812 50 Bratislava, Slovak Republic.
authors.forename: S
authors.initials: S
authors.lastname: Spanik
authors.affiliation: Biometrics, IST GmbH, Soldnerstrasse 1, 68219 Mannheim, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Ahlers
authors.affiliation: Biometrics, IST GmbH, Soldnerstrasse 1, 68219 Mannheim, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Messinger
authors.affiliation: Oncology Division, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv 64239, Israel.
authors.forename: M J
authors.initials: MJ
authors.lastname: Inbar
authors.affiliation: Clinical Division of Oncology and Department of Medicine I, Medical University of Vienna and CECOG, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Zielinski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012307:Risk Factors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human