Bevacizumab is associated with a higher gastrointestinal/genitourinary fistula or perforation risk in cervical cancer patients undergoing pelvic radiotherapy

Abstract Background Bevacizumab serves as an effective treatment in cervical cancer patients with metastatic, recurrent, or advanced disease. However, gastrointestinal (GI)/genitourinary (GU) toxicities have been observed after bevacizumab treatment. Radiotherapy (RT) is the mainstay of treatment of cervical cancer. Objectives To investigate the risk of GI/GU toxicities with bevacizumab plus RT compared with RT alone in cervical cancer patients. Search Strategy In this meta‐analysis, PubMed, Embase, Web of Science, and Cochrane databases were searched from inception to September 25, 2022. Selection Criteria Cohort studies evaluating the association between bevacizumab and GI/GU fistula or perforation in irradiated metastatic, recurrent, or advanced cervical cancer patients. Data Collection and Analysis Results are expressed as odds ratios (OR) with 95% confidence intervals (CI). The inconsistency test ( I 2 ) was used to assess heterogeneity. Egger's regression test with a two‐tailed P value was used to evaluate publication bias. Main Results Four cohort studies met the inclusion criteria with a total of 597 women included. There was a significant association between GI fistula/perforation and GU fistula/perforation in irradiated cervical cancer patients receiving bevacizumab (OR 4.03 95% CI: 1.76–9.20 and OR 4.71 95% CI: 1.51–14.70, respectively). Conclusions The bevacizumab‐containing regimen was associated with an increased risk of GI or GU toxicities in cervical cancer individuals undergoing pelvic RT. These results suggest the bevacizumab‐associated benefits and risk should be better weighted to reach an optimal treatment strategy. Further investigation on optimal dosage and timing of bevacizumab and RT is vital to minimize the adverse events and maximize the benefits.