Bevacizumab for Ovarian Cancer at High Risk of Progression: Reproducibility of Trial Results in ‘Real-world’ Patients

Patients and Methods

Consecutive patients with advanced (FIGO stage III-IV) epithelial ovarian, fallopian tube or primary peritoneal cancer, who were managed by the South West Wales Gynaecological Cancer Multidisciplinary Team based in Swansea and received at least one dose of bevacizumab as part of first-line treatment were eligible for this retrospective study. Bevacizumab was given at the dose of 7.5 mg/kg every 3 weeks, initially in combination with chemotherapy and then continued as maintenance therapy until disease progression, death or discontinuation due to side-effects. Patients were eligible for bevacizumab if considered at high risk of disease progression, i.e. if they had FIGO stage IV disease, or suboptimally debulked FIGO stage III disease. Suboptimal debulking was defined as any residual disease macroscopically visible after a procedure performed by Gynaecological Oncologists, which was planned to include a midline laparotomy, collection of ascites or washings for cytology, hysterectomy, bilateral salpingoophorectomy and supra/infracolic omentectomy. When appropriate, patients also underwent more radical procedures, including small or large bowel resections with primary anastomosis or stoma formation, gastric resection, cholecystectomy, splenectomy, peritoneal stripping of pelvis, abdomen and/or diaphragm, partial cystectomy with bladder repair or ureteric re-implantation. Debulking surgery was performed either upfront (before starting chemotherapy) or after three or more cycles of neoadjuvant chemotherapy when the initial clinical and radiological presentation predicted a low probability of achieving optimal debulking with upfront surgery in the opinion of the Multidisciplinary Team. Bevacizumab was started with the first or second postoperative chemotherapy cycle, both in patients receiving neoadjuvant chemotherapy and in those undergoing upfront debulking. After completion of chemotherapy, response was assessed radiologically and patients whose disease had not progressed according to Response Evaluation Criteria in Solid Tumors criteria (8) continued with single-agent maintenance bevacizumab every 3 weeks until symptomatic or radiological progression. Asymptomatic cancer antigen 125 (CA125) rise without radiological evidence of progression was not considered a reason for discontinuation of bevacizumab. At the time of progression, patients were offered standard second-line treatment based on their platinum-free interval; bevacizumab was not used again with second-line regimens.

Survival analysis was carried out using SPSS, version 20 (IBM Corp., Armonk, NY, USA). Progression-free survival was determined as the time from the first active treatment (debulking surgery for patients undergoing upfront debulking, or first cycle of chemotherapy for patients receiving neoadjuvant treatment) to the date of progression (radiological or symptomatic) or death (any cause), whichever occurred first. The date of last contact was recorded to censor patients who were still alive and free of progression at the time of the analysis. Due to the relatively short follow-up time, overall survival was not analysed in this study.