title: Independent review of E2100: a phase III trial of bevacizumab plus paclitaxel versus paclitaxel in women with metastatic breast cancer.
abstract: OBJECTIVE
  E2100, an open-label, randomized, phase III trial conducted by the Eastern Cooperative Oncology Group (ECOG), demonstrated a significant improvement in progression-free survival (PFS) and overall response rate (ORR) with paclitaxel plus bevacizumab compared with paclitaxel alone as initial chemotherapy for patients with HER2-negative metastatic breast cancer.
  
  
  METHODS
  An independent, blinded review of radiologic and clinical data was performed, assessing progression and response according to Response Evaluation Criteria in Solid Tumors. In addition, ECOG's investigator assessments were reanalyzed using the same methods applied to the independent review. The primary end point was PFS as assessed by an independent review facility (IRF).
  
  
  RESULTS
  The addition of bevacizumab to paclitaxel resulted in a statistically significant improvement in PFS using both the IRF and investigator assessments. Hazard ratios for PFS (0.48, 95% CI, 0.385 to 0.607; P < .0001 for the IRF v 0.42, 95% CI, 0.34 to 0.52; P < .0001 for ECOG investigators) and the improvement in median PFS (11.3 v 5.8 months for the IRF v 11.4 v 5.8 months for ECOG investigators) were similar. Among patients with measurable disease at baseline, the IRF-assessed ORR was significantly higher in patients treated with paclitaxel and bevacizumab (48.9% v 22.2%; P < .0001).
  
  
  CONCLUSIONS
  The risk of progression was reduced by more than half and the ORR more than doubled with the addition of bevacizumab to weekly paclitaxel in both analyses, confirming a substantial and robust bevacizumab treatment effect. The consistency between the IRF and ECOG analyses validates the original data previously reported by ECOG in this open-label trial.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02115, USA. gray@jimmy.harvard.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Gray
authors.forename: Suman
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Christopher
authors.initials: C
authors.lastname: Bowden
authors.forename: Kathy
authors.initials: K
authors.lastname: Miller
authors.forename: Robert L
authors.initials: RL
authors.lastname: Comis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000556:secondary; D005260:Female; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage*; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab; D017239:Paclitaxel