title: Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer.
abstract: BACKGROUND
  In an open-label, randomized, phase 3 trial, we compared the efficacy and safety of paclitaxel with that of paclitaxel plus bevacizumab, a monoclonal antibody against vascular endothelial growth factor, as initial treatment for metastatic breast cancer.
  
  
  METHODS
  We randomly assigned patients to receive 90 mg of paclitaxel per square meter of body-surface area on days 1, 8, and 15 every 4 weeks, either alone or with 10 mg of bevacizumab per kilogram of body weight on days 1 and 15. The primary end point was progression-free survival; overall survival was a secondary end point.
  
  
  RESULTS
  From December 2001 through May 2004, a total of 722 patients were enrolled. Paclitaxel plus bevacizumab significantly prolonged progression-free survival as compared with paclitaxel alone (median, 11.8 vs. 5.9 months; hazard ratio for progression, 0.60; P<0.001) and increased the objective response rate (36.9% vs. 21.2%, P<0.001). The overall survival rate, however, was similar in the two groups (median, 26.7 vs. 25.2 months; hazard ratio, 0.88; P=0.16). Grade 3 or 4 hypertension (14.8% vs. 0.0%, P<0.001), proteinuria (3.6% vs. 0.0%, P<0.001), headache (2.2% vs. 0.0%, P=0.008), and cerebrovascular ischemia (1.9% vs. 0.0%, P=0.02) were more frequent in patients receiving paclitaxel plus bevacizumab. Infection was more common in patients receiving paclitaxel plus bevacizumab (9.3% vs. 2.9%, P<0.001), but febrile neutropenia was uncommon (<1% overall).
  
  
  CONCLUSIONS
  Initial therapy of metastatic breast cancer with paclitaxel plus bevacizumab prolongs progression-free survival, but not overall survival, as compared with paclitaxel alone. (ClinicalTrials.gov number, NCT00028990 [ClinicalTrials.gov].).
authors.affiliation: Indiana University Cancer Center, Indianapolis, USA. kathmill@iupui.edu
authors.forename: Kathy
authors.initials: K
authors.lastname: Miller
authors.forename: Molin
authors.initials: M
authors.lastname: Wang
authors.forename: Julie
authors.initials: J
authors.lastname: Gralow
authors.forename: Maura
authors.initials: M
authors.lastname: Dickler
authors.forename: Melody
authors.initials: M
authors.lastname: Cobleigh
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: Tamara
authors.initials: T
authors.lastname: Shenkier
authors.forename: David
authors.initials: D
authors.lastname: Cella
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011788:Quality of Life; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D016019:Survival Analysis
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000972:Antineoplastic Agents, Phytogenic; D000068258:Bevacizumab; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases