Incidence of fistula occurrence in patients with cervical cancer treated with bevacizumab: data from real-world clinical practice

Abstract

Background This study aimed to determine the incidence of pelvic fistulas in cervical cancer patients treated with bevacizumab in Japanese clinical practice. Methods A post-marketing surveillance (PMS) study was conducted between June 2016 and February 2018 to survey physicians who treated advanced or recurrent cervical cancer patients with bevacizumab (according to the product label). The clinical/treatment status of patients with pelvic fistulas was assessed in an additional retrospective case series study. Results 142 patients were included in the PMS study (median age 51 years; 66.9% squamous cell carcinoma; 66.2% recurrent cervical cancer; 64.1% previous radiotherapy). Patients received a median of seven bevacizumab doses. Six patients, all of whom had a history of pelvic irradiation, developed seven fistulas (4.2%; 95% confidence interval, 1.56–8.96), and five patients had also undergone pelvic surgery. The case series study of the patients who developed fistulas indicated that three patients had high cumulative bladder and rectal doses of radiation, and two of them had undergone salvage re-irradiation for pelvic recurrence. The other three patients underwent both radical hysterectomy and adjuvant radiotherapy, but did not receive an excessive radiation dose to the bladder or rectum. Conclusions This study found that the upper limit of the 95% confidence interval for pelvic fistula incidence did not exceed the incidence reported in the GOG 240 study. To ensure an adequate benefit-risk assessment of bevacizumab in cervical cancer patients, a comprehensive evaluation of prior treatment is essential and the possibility of unexpected fistulas, even after careful evaluation, should be considered.

Real-world efficacy and safety of bevacizumab single-maintenance therapy following platinum-paclitaxel chemotherapy plus bevacizumab in patients with advanced cervical cancer

“…This outcome was similar to that of the CECILIA study (11.3%) [ 16 ] and a multicenter study in the Kinki district of Japan (11.2%) [ 19 ]. A medical history of pelvic radiotherapy was considered a risk factor for fistula and intestinal perforation, as previously reported [ 2 4 16 19 20 ]. These studies reported that the rate of fistula formation or intestinal perforation in previously irradiated patients was 84%–100%.…”