RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer

J Clin Oncol. 2011 Apr 1;29(10):1252-60. doi: 10.1200/JCO.2010.28.0982. Epub 2011 Mar 7.


Purpose: This phase III study compared the efficacy and safety of bevacizumab (BV) when combined with several standard chemotherapy regimens versus those regimens alone for first-line treatment of patients with human epidermal growth factor receptor 2-negative metastatic breast cancer.

Patients and methods: Patients were randomly assigned in 2:1 ratio to chemotherapy plus BV or chemotherapy plus placebo. Before random assignment, investigators chose capecitabine (Cape; 2,000 mg/m(2) for 14 days), taxane (Tax) -based (nab-paclitaxel 260 mg/m(2), docetaxel 75 or 100 mg/m(2)), or anthracycline (Anthra) -based (doxorubicin or epirubicin combinations [doxorubicin/cyclophosphamide, epirubicin/cyclophosphamide, fluorouracil/epirubicin/cyclophosphamide, or fluorouracil/doxorubicin/cyclophosphamide]) chemotherapy administered every 3 weeks. BV or placebo was administered at 15 mg/kg every 3 weeks. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), 1-year survival rate, objective response rate, duration of objective response, and safety. Two independently powered cohorts defined by the choice of chemotherapy (Cape patients or pooled Tax/Anthra patients) were analyzed in parallel.

Results: RIBBON-1 (Regimens in Bevacizumab for Breast Oncology) enrolled 1,237 patients (Cape cohort, n = 615; Tax/Anthra cohort, n = 622). Median PFS was longer for each BV combination (Cape cohort: increased from 5.7 months to 8.6 months; hazard ratio [HR], 0.69; 95% CI, 0.56 to 0.84; log-rank P < .001; and Tax/Anthra cohort: increased from 8.0 months to 9.2 months; HR, 0.64; 95% CI, 0.52 to 0.80; log-rank P < .001). No statistically significant differences in OS between the placebo- and BV-containing arms were observed. Safety was consistent with results of prior BV trials.

Conclusion: The combination of BV with Cape, Tax, or Anthra improves clinical benefit in terms of increased PFS in first-line treatment of metastatic breast cancer, with a safety profile comparable to prior phase III studies.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Webcast

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / secondary
  • Chi-Square Distribution
  • Disease-Free Survival
  • Double-Blind Method
  • Europe
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Recurrence, Local*
  • Placebo Effect
  • Proportional Hazards Models
  • Receptor, ErbB-2 / analysis*
  • Risk Assessment
  • Risk Factors
  • Survival Rate
  • Time Factors
  • Treatment Outcome
  • United States
  • Young Adult


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • Bevacizumab
  • ERBB2 protein, human
  • Receptor, ErbB-2