Osteonecrosis of the Jaw (ONJ) Associated with Bevacizumab: A Case Series from the FDA Adverse Event Reporting System (FAERS) Database

Abstract Introduction: Osteonecrosis of the jaw (ONJ) is a rare but serious adverse drug reaction (ADR) historically associated with denosumab and bisphosphonate therapy. Studies have demonstrated an association between ONJ and bevacizumab, a VEGF inhibitor now used for a variety of malignancies. This study reviewed cases of bevacizumab associated ONJ reported to the FDA Adverse Event Reporting System (FAERS) database Methods: The FAERS database was searched for all reported cases of ONJ from 2010 to 2021. A dataset was created for bevacizumab-associated ONJ and demographics were summarized. Only adults (age 18 and older) and reports from healthcare professionals were included for analysis. Duplicate cases were removed. Cases lacking information on patient age or gender were excluded from review. A subgroup analysis was performed for subjects receiving bevacizumab without prior or concomitant denosumab or bisphosphonate therapy. Results: 19,670 cases of ONJ were reported to the FAERS database between 2010 to 2021 with approximately half (9,556) containing complete patient demographic data. 146 cases (1.5% of the total) of bevacizumab-associated ONJ were identified. 96 (65.8%) of the patients were female and the average age was 60.9 years +/- 9.3 years. There were 34 cases without prior or concomitant bisphosphonate or denosumab therapy. Male gender occurred in 65% (22 of 34) of these cases and average age was 61 years +/- 12.0. Table/Figure 1 depicts clinical indications for each of these 34 cases. Gastrointestinal malignancies (i.e., colon cancer and esophageal cancer) were present in 6/34 (17.6%) cases without prior denosumab/bisphosphonate therapy, 5 patients of breast cancer (14.7%) and 5 cases of prostate cancer were also noted(14.7%). Discussion: 146 cases of bevacizumab-associated ONJ have been reported to the FAERS database and 23% of these cases did not involve medications known to cause ONJ. GI malignancy was the most common primary malignancy for reports of bevacizumab-associated ONJ. Clinicians should consider ONJ as a potential adverse effect in patients with malignancies that are being treated with bevacizumab.