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

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 antiangiogenic 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

Osteonecrosis of jaw beyond antiresorptive (bone-targeted) agents: new horizons in oncology

“…ONJ cases after bevacizumab alone were observed in colorectal, breast, lung, parotid gland, and renal cancer patients, and revealed differentiated clinical history and outcome. [12,18,[71][72][73][74][75][76] Furthermore, one case was observed after intravitreous bevacizumab. [77] Some other published cases are notable: one pancreatic cancer patient showed ONJ during treatment with bevacizumab and sorafenib [78] and one renal cell cancer patient had received bevacizumab plus temsirolimus [79]; another renal cell cancer patient developed ONJ during bevacizumab treatment, after previous treatments with sunitinib and temsirolimus.…”

“…We have already reported the initial experience from Memorial Sloan Kettering Cancer Center. [51] In 2010, a retrospective study on breast cancer patients revealed a very low risk after bevacizumab alone (0.3-04%) in comparison with the combination of bevacizumab and BPs (0.9-2.4% range) within a large trial population [12] However, only ONJ cases with frank bone exposure were registered in that analysis, and median follow-up of groups ranged only between 10 and 19 months. Were ONJ cases in bevacizumab-treated patients somewhat different from BRONJ cases?…”

“…The first case report associating bevacizumab with the onset of ONJ was published in 2008 [11]; subsequently, it was retrospectively analyzed for the data of safety on the use of bevacizumab in improving the clinical outcome of patients with breast cancer (ATHENA, AVADO, and RIBBON-1) [12] demonstrating that the concomitant use of bevacizumab plus intravenous BPs significantly increased the risk of ONJ compared with the use of bevacizumab or BP alone. The same mechanism that underlies the hypothetical pathogenesis of ONJ with the use of bevacizumab may be shifted to the administration of TKIs in particular with sunitinib in metastatic renal carcinoma and gastro intestinal stromal tumor (GIST).…”

Medication-Related Osteonecrosis of the Jaws (MRONJ) Induced by Incompatible Complete Removable Denture: A Case Report

“…Recently, it is reported that osteonecrosis of jaws cases associated with other antiresorptive (denosumab) and antiangiogenic therapies increase gradually. [15] Therefore, a change was needed to accommodate the term of BRONJ. In 2014, American Association of Oral and Maxillofacial Surgeons (AAOMS) recommended that the term "Bisphosphonate-related Osteonecrosis of The Jaw" (BRONJ) be replaced with the new terminology ''Medication-related Osteonecrosis of the Jaw'' (MRONJ).…”

Osteochemonecrosis: An Overview

“…VEGF inhibitors work somewhat more directly to inhibit the osteoclasts through their action on monocytes which then are in the osteoclast developmental feedback loop. Further reading on these medications will be left to the reader for exploration [30][31][32][33][34][35][36][37][38][39][40].…”