Breast Cancer Research and Treatment

, Volume 122, Issue 1, pp 181–188

Bevacizumab and osteonecrosis of the jaw: incidence and association with bisphosphonate therapy in three large prospective trials in advanced breast cancer

  • Valentina Guarneri
  • David Miles
  • Nicholas Robert
  • Véronique Diéras
  • John Glaspy
  • Ian Smith
  • Christoph Thomssen
  • Laura Biganzoli
  • Tanya Taran
  • PierFranco Conte
Clinical trial


Long-term bisphosphonate therapy is associated with increased risk of osteonecrosis of the jaw (ONJ). In a retrospective analysis, a 16% ONJ incidence was reported in patients receiving bisphosphonates with anti-angiogenic therapy (bevacizumab or sunitinib) for bone metastases from breast, colon, or renal cell cancers. To assess ONJ incidence with bevacizumab, we analysed data from 3,560 patients receiving bevacizumab-containing therapy for locally recurrent or metastatic breast cancer (LR/MBC) in two double-blind, randomised trials (AVADO and RIBBON-1) and a large, non-randomised safety study (ATHENA). The overall incidence of ONJ with bevacizumab was 0.3% in the blinded phase of the two randomised trials and 0.4% in the single-arm study. There was a trend towards increased ONJ incidence in patients who received bisphosphonate therapy versus those with no bisphosphonate exposure (0.9 vs. 0.2%, respectively, in the pooled analysis of the randomised trials; 2.4 vs. 0%, respectively, in ATHENA). In conclusion, this is the largest analysis of ONJ in patients receiving bevacizumab for LR/MBC. The 0.3–0.4% incidence is considerably lower than previously suggested with anti-angiogenic therapy in a small retrospective analysis. The risk of ONJ appeared to be increased in patients exposed to bisphosphonates, a pattern consistent with observations before the introduction of anti-angiogenic therapy to breast cancer management. The 0.9–2.4% incidence seen in bisphosphonate-exposed patients receiving bevacizumab is within the 1–6% range reported for bisphosphonates alone. Good oral hygiene, dental examination, and avoidance of invasive dental procedures remain important in patients receiving bisphosphonates, irrespective of bevacizumab administration.


Osteonecrosis of the jaw Bisphosphonate Angiogenesis Bevacizumab Metastatic breast cancer 





Locally recurrent or metastatic breast cancer


Memorial Sloan-Kettering Cancer Center


Osteonecrosis of the jaw


Vascular endothelial growth factor


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Valentina Guarneri
    • 1
  • David Miles
    • 2
  • Nicholas Robert
    • 3
  • Véronique Diéras
    • 4
  • John Glaspy
    • 5
  • Ian Smith
    • 6
  • Christoph Thomssen
    • 7
  • Laura Biganzoli
    • 8
  • Tanya Taran
    • 9
  • PierFranco Conte
    • 1
  1. 1.Department of Oncology, Hematology and Respiratory DiseasesUniversity of Modena and Reggio Emilia, University HospitalModenaItaly
  2. 2.Mount Vernon Cancer CentreNorthwoodUK
  3. 3.US OncologyFairfax Northern Virginia Hematology OncologyFairfaxUSA
  4. 4.Institut CurieParisFrance
  5. 5.Los Angeles School of Medicine TORI NetworkUniversity of CaliforniaLos AngelesUSA
  6. 6.Royal Marsden Hospital and Institute of Cancer ResearchLondonUK
  7. 7.Martin-Luther-Universitaet Halle-WittenbergHalle (Saale)Germany
  8. 8.Prato Hospital, Istituto Toscano TumoriPratoItaly
  9. 9.F. Hoffmann-La Roche Ltd.BaselSwitzerland

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