Risk Factors for Gastrointestinal Adverse Events Studied in Setting of First-Line Bevacizumab/Chemotherapy for Ovarian Cancer
As reported in the Journal of Clinical Oncology, Burger et al assessed risk factors for gastrointestinal adverse events in women with advanced ovarian cancer receiving first-line bevacizumab (Avastin)/chemotherapy with or without bevacizumab maintenance or chemotherapy alone in the phase III Gynecologic Oncology Group (GOG) 0218 trial. Bevacizumab treatment, history of treatment for inflammatory bowel disease, and receipt of large bowel resection at primary surgery were associated with increased risk. Risk did not appear to be increased by bevacizumab maintenance.
Study Details
In the GOG 0218 trial, women with previously untreated advanced disease after surgery were randomly assigned to six cycles of platinum/taxane chemotherapy plus placebo during cycles 2 to 22 (n = 625), chemotherapy plus bevacizumab in cycles 2 to 6 and placebo in cycles 7 to 22 (n = 625), or chemotherapy plus bevacizumab in cycles 2 to 22 (n = 623). Patients were assessed for gastrointestinal adverse events consisting of grade ≥ 2 perforation, fistula, necrosis, or hemorrhage.
Among 1,759 evaluable patients (94% of total), 50 (2.8%) had a gastrointestinal adverse event, including 10 (1.7%) of 587 patients receiving chemotherapy plus placebo maintenance, 20 (3.4%) of 587 receiving bevacizumab/chemotherapy plus placebo maintenance, and 20 (3.4%) of 585 receiving bevacizumab/chemotherapy plus bevacizumab maintenance.
Significant Risk Factors
On univariate analysis, history of inflammatory bowel disease (P = .020) or treatment of inflammatory bowel disease (P = .005), small bowel resection with anastomosis (P = .039) or at primary surgery (P = .032), and large bowel resection with anastomosis (P = .016) or at primary surgery (P = .012) were significantly associated with risk for gastrointestinal adverse events.
In a multivariable logistic model adjusting for inflammatory bowel disease treatment, small bowel resection at primary surgery, and large bowel resection at primary surgery, odds ratios (ORs) for gastrointestinal adverse events were 2.15 (95% confidence interval [CI] = 0.981–4.71) in the bevacizumab/chemotherapy plus placebo maintenance group and 2.15 (95% CI = 0.981–4.70) in the bevacizumab/chemotherapy plus bevacizumab maintenance group vs the chemotherapy alone plus placebo maintenance group.
On multivariate analysis that combined the two bevacizumab groups, receipt of bevacizumab was associated with a significantly increased risk of gastrointestinal adverse events (OR = 2.15, P = .032). Treatment for inflammatory bowel disease (OR = 13.40, P < .001) and large bowel resection at primary surgery (OR = 2.05, P = .026) were also associated with significantly increased risk.
The investigators concluded, “History of treatment for [inflammatory bowel disease], and bowel resection at primary surgery, increase the odds of [gastrointestinal adverse events] in patients receiving first-line platinum-taxane chemotherapy for advanced ovarian cancer. After accounting for these risk factors, concurrent bevacizumab doubles the odds of a [gastrointestinal adverse event], but is not appreciably increased by continuation beyond chemotherapy.”
Robert A. Burger, MD, of the University of Pennsylvania School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by grants from the National Cancer Institute. The study authors reported no potential conflicts of interest.
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