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

Breast Cancer Res Treat. 2010 Jul;122(1):181-8. doi: 10.1007/s10549-010-0866-3. Epub 2010 Apr 2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects*
  • Angiogenesis Inhibitors / therapeutic use
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab
  • Breast Neoplasms / complications
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Diphosphonates / adverse effects*
  • Docetaxel
  • Double-Blind Method
  • Drug Synergism
  • Female
  • Genes, erbB-2
  • Humans
  • Incidence
  • Jaw Diseases / chemically induced*
  • Jaw Diseases / epidemiology
  • Jaw Diseases / prevention & control
  • Middle Aged
  • Multicenter Studies as Topic / statistics & numerical data*
  • Neoplasm Metastasis
  • Oral Hygiene
  • Osteonecrosis / chemically induced*
  • Osteonecrosis / epidemiology
  • Osteonecrosis / prevention & control
  • Paclitaxel / administration & dosage
  • Prospective Studies
  • Randomized Controlled Trials as Topic / statistics & numerical data*
  • Taxoids / administration & dosage
  • Vinblastine / administration & dosage
  • Vinblastine / analogs & derivatives
  • Vinorelbine

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Diphosphonates
  • Taxoids
  • Docetaxel
  • Bevacizumab
  • Vinblastine
  • Paclitaxel
  • Vinorelbine