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

Valentina Guarneri (1) , David W. 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 Department of Oncology, Hematology and Respiratory Diseases
2 Mount Vernon Cancer Centre
3 US Oncology
4 Institut Curie [Paris]
5 Los Angeles School of Medicine TORI Network
6 Royal Marsden Hospital and Institute of Cancer Research
7 MLU - Martin-Luther-Universität Halle Wittenberg
8 Prato Hospital, Istituto Toscano Tumori
9 F. Hoffmann-La Roche [Basel]

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.

Mots clés: Osteonecrosis of the jaw; Bisphosphonate; Angiogenesis; Bevacizumab; Metastatic breast cancer

Valentina Guarneri, David W. Miles, Nicholas Robert, Véronique Diéras, John Glaspy, 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 Research and Treatment, 2010, 122 (1), pp.181-188. ⟨10.1007/s10549-010-0866-3⟩. ⟨hal-00535451⟩