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

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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.

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Abbreviations

5-FU:

5-Fluorouracil

LR/MBC:

Locally recurrent or metastatic breast cancer

MSKCC:

Memorial Sloan-Kettering Cancer Center

ONJ:

Osteonecrosis of the jaw

VEGF:

Vascular endothelial growth factor

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Acknowledgments

The three trials included in these analyses (AVADO, RIBBON-1 and ATHENA) were sponsored by F. Hoffmann-La Roche Ltd., Basel, Switzerland (AVADO, ATHENA) and Genentech Inc., South San Francisco, CA, USA (RIBBON-1). F. Hoffmann-La Roche Ltd. provided statistical support for the analyses described in this article and funded medical writing support provided by Jennifer Kelly.

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Authors and Affiliations

  1. Department of Oncology, Hematology and Respiratory Diseases, University of Modena and Reggio Emilia, University Hospital, Via del Pozzo 71, 41100, Modena, Italy

    Valentina Guarneri & PierFranco Conte

  2. Mount Vernon Cancer Centre, Northwood, UK

    David Miles

  3. US Oncology, Fairfax Northern Virginia Hematology Oncology, Fairfax, VA, USA

    Nicholas Robert

  4. Institut Curie, Paris, France

    Véronique Diéras

  5. Los Angeles School of Medicine TORI Network, University of California, Los Angeles, CA, USA

    John Glaspy

  6. Royal Marsden Hospital and Institute of Cancer Research, London, UK

    Ian Smith

  7. Martin-Luther-Universitaet Halle-Wittenberg, Halle (Saale), Germany

    Christoph Thomssen

  8. Prato Hospital, Istituto Toscano Tumori, Prato, Italy

    Laura Biganzoli

  9. F. Hoffmann-La Roche Ltd., Basel, Switzerland

    Tanya Taran

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  1. Valentina Guarneri
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Correspondence to Valentina Guarneri.

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Guarneri, V., Miles, D., Robert, N. et al. 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 122, 181–188 (2010). https://doi.org/10.1007/s10549-010-0866-3

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