Analysis of Bevacizumab (Bev) Therapy, Bisphosphonate Use and Osteonecrosis of the Jaw (ONJ) in >1900 Patients Treated in Two Randomized, Controlled Trials.

Abstract

Abstract Background: Long-term bisphosphonate therapy is known to increase the risk of ONJ. A 16% incidence of ONJ was reported in a retrospective analysis of 116 patients receiving bisphosphonates with anti-angiogenic therapy (Bev or sunitinib) for bone metastases from breast, colon, or renal cell cancers.Methods: To assess the incidence of ONJ with Bev, we analyzed data from >3500 patients with locally recurrent or metastatic breast cancer (LR/MBC) treated in three large trials of Bev-containing therapy: AVADO (Bev in combination with docetaxel); RIBBON-1 (Bev in combination with taxane, anthracycline-based combination therapy, or capecitabine); and MO19391 (single-arm safety study of >2000 patients receiving Bev-containing therapy in the general oncology practice context). The incidence of ONJ was compared in patients treated with Bev versus placebo and in patients with or without bisphosphonate exposure.Results: Data from the blinded phase of two randomized, placebo-controlled trials demonstrated an ONJ incidence of 0.3%. ONJ was more common in patients who also received bisphosphonate therapy than in those who received no bisphosphonates (Table). This observation is supported by data from 2216 patients treated in the single-arm MO19391 study (2.4% with bisphosphonate versus 0% without). AVADO*RIBBON-1**TotalIncidence of ONJ, no. of pts (%)Bev (n=492)Pla (n=238)Bev (n=817)Pla (n=412)Bev (n=1309)Pla (n=650)Overall population receiving Bev (n=1309)3 (0.6%)O1 (0.1%)O4 (0.3%)OBisphosphonate (n=233)1 (1.2%)O1 (0.6%)O2 (0.9%)ONo bisphosphonate (n=1076)2 (0.5%)OOO2 (0.2%)O *Bev 15 and 7.5 mg/kg arms pooled**Taxane/anthracycline and capecitabine cohorts pooledConclusions: This is the largest analysis of ONJ in patients receiving Bev for LR/MBC. The 0.3% incidence of ONJ with Bev is considerably lower than previously reported by Christodoulou et al. with anti-angiogenic therapy. As in the general population, the risk of ONJ is increased in patients exposed to bisphosphonates. The 0.9–2.4% incidence seen here in a large population of patients receiving Bev and bisphosphonate therapy is substantially lower than the 16% observed in a small cohort of patients from a retrospective analysis and within the range reported in the literature for bisphosphonates alone (1–4%). Good oral hygiene, dental examination and avoidance of invasive dental procedures remain important in patients receiving bisphosphonates, irrespective of Bev treatment. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 208.