Bevacizumab and Gastrointestinal Perforations

A Review From the FDA Adverse Event Reporting System (FAERS) Database

Thomas A. Wichelmann; Sufyan Abdulmujeeb; Eli D. Ehrenpreis

Disclosures

Aliment Pharmacol Ther. 2021;54(10):1290-1297. 

In This Article

Results

The calculated reporting odds ratio of bevacizumab-induced GI perforations was 33.33 (32.05–34.66, 95% CI). A total of 1648 cases met inclusion/exclusion criteria and 1375 cases remained after the removal of duplicates (see Figure 1). In total, 702 cases (51.1%) were female and the average age was 61.9 years old ± 11.4 years (see Figure 2 for age distribution) with 45.5% of cases (625 of 1375) occurring in individuals aged 65 and older.

Figure 1.

Over 74 000 cases of bevacizumab-induced ADRs were identified from 2004 to July, 2021 within the FAERS database. 2874 cases of bevacizumab-induced gastrointestinal perforation were selected for review. This figure illustrates the various reasons for case exclusion highlighted in the red boxes as well as the number of remaining duplicate cases that were removed from analysis

Figure 2.

This graph represents the age breakdown of bevacizumab-induced gastrointestinal perforations cases that were reported in the FAERS database from 2004 to July, 2021

All cases were defined by either nonspecific or specific location of perforation (see Table 3). Nonspecific sites of perforation were reported as "Gastrointestinal perforation" (379 cases, 29.5%) or "Intestinal perforation" (298 cases, 23.2%). Nonspecific sites (677 of 1375) represented 49.2% of all cases that met inclusion and exclusion criteria. When specific locations were included in the reports, there were 385 reports of colorectal perforations (55.2% of specific description cases), 251 small intestine perforations (36.0% of specific description cases), and 62 gastro-oesophageal perforations (8.9% of specific description cases) (see Appendix A4).

The three most common primary malignancies in reports of bevacizumab-induced GI perforations were colorectal cancer (691 cases, 50.3%), ovarian cancer (197 cases, 14.3%), and NSCLC (182 cases, 13.2%) (see Table 1). Colorectal cancer-associated bevacizumab-induced GI perforations average age was 62.7 ± 11.4 years. Specific locations of perforation were reported in 345 cases (49.9%) of subjects with colorectal cancer. Ovarian cancer-associated bevacizumab-induced GI perforations average age was 59.8 ± 11.1 years. Specific locations of perforations were reported in 78 cases (41.1%) of subjects with ovarian cancer. NSCLC-associated bevacizumab-induced GI perforations average age was 64.7 ± 9.7 years. Specific locations of perforations were reported in 82 cases (45.1%) of subjects with NSCLC. See Figure 3 for perforation location descriptions among the top three indications for bevacizumab use associated with GI perforation within the FAERS database.

Figure 3.

The locations of GI perforation associated with the top three indications for bevacizumab use contained within the FAERS database are illustrated in this figure

The average age of colorectal cancer patients with bevacizumab-induced GI perforation (62.7 ± 11.4 years) was significantly different from the average age of ovarian cancer patients with bevacizumab-induced GI perforation (59.8 ± 11.1 years; P < 0.005). Similarly, the average age of ovarian cancer patients with bevacizumab-induced GI perforation (59.8 ± 11.1 years) was significantly different from the average age of NSCLC patients with bevacizumab-induced GI perforation (64.7 ± 9.7 years; P < 0.0001). Finally, the average age of colorectal cancer patients with bevacizumab-induced GI perforation compared to patients with NSCLC (62.7 ± 11.4 years and 64.7 ± 9.7 years, respectively) was significantly different (P < 0.05).

Death was reported in 554 patients (40.3% of total cases). The average age among patients who died was 62.8 ± 11.6 years. The three most common indications for use in patients who died were colorectal cancer (262 cases, 47.3%), ovarian cancer (85 cases, 15.3%) and NSCLC (66 cases, 11.9%) (see Table 2). Death occurred in 37.9% of colorectal cancer cases, 43.2% of ovarian cancer cases and 36.3% of NSCLC cases. The average age of patients with bevacizumab-induced GI perforation who had colorectal cancer and died was 63.8 ± 10.8 years. 58.0% (152/262) were male. The average age of patients with bevacizumab-induced GI perforation who had ovarian cancer and died was 60.1 ± 12.2 years. The average age of patients with bevacizumab-induced GI perforation who had NSCLC and died was 65.7 ± 9.7 years. 80.3% (53/66) were male.

There were 62 cases of gastro-oesophageal region perforations (11 located in the oesophagus and 51 located in the stomach). The average age was 62.4 years of age ± 14.2 years. 66.1% of these patients were male (41 cases) and 33.9% were female (21 cases) (see Appendix A5). Mortality occurred in 18 cases (29.0%) (see Appendix A5). The three most common indications for use were colorectal cancer (31 cases, 50.0% of subgroup), gastric cancer (9 cases, 14.5% of subgroup), and NSCLC (5 cases, 8.1% of subgroup) (see Appendix A4 and A5).

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