title: Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer.
abstract: OBJECTIVE
  The efficacy and safety of combining bevacizumab (7.5 and 15 mg/kg) with docetaxel as first-line therapy for human epidermal growth factor receptor 2 (HER2) -negative, locally recurrent or metastatic breast cancer (MBC) was investigated in a three-arm, placebo-controlled, phase III trial.
  
  
  METHODS
  Patients (N = 736) were randomly assigned to docetaxel 100 mg/m(2) plus either placebo or bevacizumab 7.5 or 15 mg/kg every 3 weeks. The primary end point was progression-free survival (PFS); secondary end points included best overall response, duration of response, time to treatment failure, overall survival, and safety.
  
  
  RESULTS
  Combination of bevacizumab 15 mg/kg, but not 7.5 mg/kg, with docetaxel showed superior median PFS (mPFS) to placebo plus docetaxel in unstratified analysis (placebo mPFS, 8.2 months; 7.5 mg/kg mPFS, 9.0 months [hazard ratio (HR), 0.86; P = .12]; 15 mg/kg mPFS, 10.1 months [HR, 0.77; P = .006]) and stratified analysis (placebo mPFS, 8.1 months; 7.5 mg/kg mPFS, 9.0 months [HR, 0.80; P = .045]; 15 mg/kg mPFS, 10.0 months [HR, 0.67; P < .001]). Response rates in patients with measurable disease at baseline also increased with bevacizumab 15 mg/kg (46% [placebo] v 55% [7.5 mg/kg; P = .07] and 64% [15 mg/kg; P < .001]). Combination with bevacizumab had limited impact on the known toxicity profile of docetaxel.
  
  
  CONCLUSIONS
  Combination of bevacizumab with docetaxel did not significantly impact on the safety profile of docetaxel. Bevacizumab 15 mg/kg every 3 weeks significantly increased PFS when combined with docetaxel as first-line therapy for MBC compared with docetaxel plus placebo.
authors.affiliation: Mount Vernon Cancer Centre, Mount Vernon Hospital, Northwood, Middlesex, United Kingdom. david.miles@doctors.org.uk
authors.forename: David W
authors.initials: DW
authors.lastname: Miles
authors.forename: Arlene
authors.initials: A
authors.lastname: Chan
authors.forename: Luc Y
authors.initials: LY
authors.lastname: Dirix
authors.forename: Javier
authors.initials: J
authors.lastname: Cortés
authors.forename: Xavier
authors.initials: X
authors.lastname: Pivot
authors.forename: Piotr
authors.initials: P
authors.lastname: Tomczak
authors.forename: Thierry
authors.initials: T
authors.lastname: Delozier
authors.forename: Joo Hyuk
authors.initials: JH
authors.lastname: Sohn
authors.forename: Louise
authors.initials: L
authors.lastname: Provencher
authors.forename: Fabio
authors.initials: F
authors.lastname: Puglisi
authors.forename: Nadia
authors.initials: N
authors.lastname: Harbeck
authors.forename: Guenther G
authors.initials: GG
authors.lastname: Steger
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Wardley
authors.forename: Andreas
authors.initials: A
authors.lastname: Chlistalla
authors.forename: Gilles
authors.initials: G
authors.lastname: Romieu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000077143:Docetaxel; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D010919:Placebos / Q000008:administration & dosage; D043823:Taxoids / Q000008:administration & dosage*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D010919:Placebos; D043823:Taxoids; D000077143:Docetaxel; D000068258:Bevacizumab; D066246:ErbB Receptors