Exploring The Link Between Bevacizumab And Gastrointestinal Perforations Using The Fda Adverse Event Reporting System Database

INTRODUCTION: Bevacizumab has demonstrated success in treating advanced malignancies. However, bevacizumab may rarely cause the potentially fatal complication of gastrointestinal (GI) perforation. To date, no large descriptive studies have characterized patients with bevacizumab-induced GI perforations. Further, the largest retrospective case series on this association identified only two cases of gastroesophageal perforation. This study reviewed reports of bevacizumab-induced GI perforations to the FDA Adverse Event Reporting System (FAERS) database. METHODS: We downloaded all reported cases of bevacizumab-associated GI perforations in the FAERS database from 2004 to present. Our dataset excluded cases lacking reported patient age, gender, location of perforation, and indication for bevacizumab use. Only reports from Healthcare Professions were included for review and all duplicate cases were removed. RESULTS: 2641 cases were reported to FAERS. 1505 cases met inclusion/exclusion criteria, and 1283 reported cases remained after removal of duplicates. 50.8% of patients were female and average patient age was 62 years old. Figure 1 shows the age distribution of reported cases. Death was reported in 513 patients (40%). The most common indications in patients with bevacizumab-induced perforations were colorectal cancer (659, 51.4%), non-small cell lung cancer (241, 18.8%) and ovarian cancer (170, 13.3%) (Figure 2). Non-specific sites of perforation were most commonly reported as “Gastrointestinal perforation” (347, 27%) or “Intestinal perforation” (278, 22%). This represented half of all cases that met inclusion/exclusion criteria. When descriptive locations were used in reporting, analysis based on location revealed 365 colorectal perforations (56%), 231 small intestine perforations (35%), and 60 gastroesophageal perforations (9%) (Figure 3). Subgroup analysis of gastroesophageal perforations yielded similar results for average age (62), however, 65% of cases were male, 32% resulted in death, and a higher proportion indicated gastric and pancreatic cancers (8% and 15% respectively) for use.Figure 1.: This graph represents the age breakdown of bevacizumab-associated gastrointestinal perforations cases that were reported in the FAERS database from 2004 to present.Figure 2.: This table represents the top 10 most common types of primary cancer in cases reported to the FAERS database with bevacizumab-associated gastrointestinal perforations. This represents approximately 95% of all cases that met inclusion and exclusion criteria.Figure 3.: This table represents the various locations/types of gastrointestinal perforations associated with bevacizumab use as reported to the FAERS database.CONCLUSION: Bevacizumab-induced GI perforations are commonly fatal and are generally seen in older patients. Reported perforations are most commonly in the large and small intestine. This study represents the largest reported series of gastroesophageal perforations associated with bevacizumab therapy.