Ovarian cancer patients had a twofold greater risk of gastrointestinal adverse effects when bevacizumab was added to chemotherapy, but the angiogenesis inhibitor did not exacerbate other known risks for GI events, data from a large prospective trial showed.
Treatment with bevacizumab was associated with a 3.4% incidence of grade 2+ GI adverse events, compared with 1.7% in patients who received only chemotherapy.
Most bevacizumab-associated GI events occurred during concomitant chemotherapy and not during bevacizumab maintenance.
Bevacizumab did not add to other known risks for grade 2+ GI adverse events, according to a presentation here at the Society of Gynecologic Oncology meeting.
“A logistic model … showed no evidence that bevacizumab treatment further increases the odds of GI adverse events associated with diagnosis of inflammatory bowel disease [IBD], medication or surgery for IBD, small-bowel resection at primary surgery, or large-bowel resection at primary surgery,” said Robert A. Burger, MD, of Fox Chase Cancer Center in Philadelphia.
Bevacizumab has demonstrated efficacy in several types of cancer when combined with standard chemotherapy. GI perforation is a known adverse effect of bevacizumab, but the risk had not been examined in a prospective trial, Burger noted.
The Gynecologic Oncology Group (GOG) 0218 trial showed that the addition of bevacizumab to front-line paclitaxel-carboplatin chemotherapy improved progression-free survival compared with chemotherapy alone in stage III-IV ovarian cancer. Additionally, GOG-0218 included a prospective analysis of potential risk factors for grade 2+ GI adverse events (perforation, anastomotic leak, fistula, necrosis, or hemorrhage).
Investigators in GOG-0218 randomized 1,800 patients to three treatment strategies: paclitaxel-carboplatin chemotherapy plus bevacizumab, followed by bevacizumab maintenance; chemotherapy plus bevacizumab and placebo maintenance; and chemotherapy plus placebo, plus placebo maintenance.
Burger reported 1.7% incidence of all grade 2+ GI adverse events combined in patients treated with chemotherapy plus placebo. Both bevacizumab groups had an incidence of 3.4%. Almost all of the adverse events occurred during treatment cycles two through six, when bevacizumab or placebo was administered with chemotherapy.
In a logistic regression model, only three factors retained statistical significance for predicting grade 2+ GI adverse events:
•Bevacizumab treatment, OR 2.15 (1.05 to 4.40)
•Treatment for IBD, OR 13.4 (3.44 to 52.3)
•Large-bowel resection at primary surgery, OR 2.05 (1.09 to 3.88)
An analysis of interaction produced no evidence that bevacizumab increased the odds of GI adverse events associated with a diagnosis of IBD, treatment of IBD, small-bowel resection at primary surgery, or large-bowel resection at primary surgery.
Invited discussant David M. O’Malley, MD, of Ohio State University in Columbus, noted that any appraisal of GI adverse events in GOG-0218 should keep in mind that the addition of bevacizumab to chemotherapy improved PFS by less than a month compared with chemotherapy alone.
O’Malley also pointed out that GI adverse events occurred infrequently (53 total) and that three of those had incomplete data, including one fatal GI bleed, and a grade 5 bowel necrosis.
“It’s only three events, but that’s still 6% of the total,” said O’Malley.
Burger RA, et al “Prospective investigation of risk factors for gastrointestinal adverse events in a phase III randomized trial of bevacizumab in first-line therapy for advanced epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer: A Gynecologic Oncology Group study” SGO 2011; Abstract 7.
Adapted from MedPage Today.