ONJ Less Than 1% With Bevacizumab


SAN ANTONIO — The largest-ever analysis of osteonecrosis of the jaw occurring in women receiving the antiangiogenesis agent bevacizumab for advanced breast cancer indicates the incidence is less than 1%, even in patients receiving bisphosphonates.

The analysis involved more than 3,500 bevacizumab-treated women with locally recurrent or metastatic breast cancer prospectively followed in large clinical trials.

As such, it provides a much more accurate—and reassuring—risk estimate than the 16% incidence recently reported by Greek investigators in patients on a bisphosphonate plus bevacizumab (Avastin) or another antiangiogenesis agent, sunitinib (Sutent), for various advanced cancers (Oncology 2009;76:209-11).

The Greek report was a retrospective analysis based on 116 bisphosphonate-treated patients, only a subset of whom were on an antiangiogenesis agent, Dr. Valentina Guarneri noted at the San Antonio Breast Cancer Symposium.

In contrast, she reported on 3,560 patients on bevacizumab combined with a taxane or other standard chemotherapy as first-line treatment for locally recurrent or metastatic breast cancer. The women were participants in the open-label ATHENA study or the randomized RIBBON-1 or AVADO trials.

In the randomized trials, the incidence of osteonecrosis of the jaw (ONJ) was 0.3% in patients on bevacizumab and zero with placebo during follow-up of 10-19 months. In ATHENA, the incidence was 0.4% during 13 months of follow-up of more than 2,200 women on bevacizumab.

The incidence of ONJ was higher in bevacizumab-treated patients with prior or current exposure to bisphosphonates, but not close to the 16% figure cited in the small Greek study. In ATHENA, the incidence of ONJ was 2.4% in bevacizumab-treated patients who had been exposed to bisphosphonates and zero in those who had not.

In the two randomized trials, the rate was 0.9% in patients who had been on a bisphosphonate, compared with 0.2% in those who had not, according to Dr. Guarneri of the University of Modena and Reggio Emilia (Italy).

Detailed analysis of all ONJ cases in this series showed that dental/oral hygiene issues—a recent extraction, a loose tooth, maxillary fracture repair—were present in one-third. Thus, dental examination and avoidance of invasive dental procedures are important in patients on intravenous bisphosphonates, regardless of whether they're on bevacizumab, she added.

Disclosures: This study was funded by F. Hoffmann-La Roche Ltd.

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