title: Risk factors for GI adverse events in a phase III randomized trial of bevacizumab in first-line therapy of advanced ovarian cancer: A Gynecologic Oncology Group Study.
abstract: OBJECTIVE
  To evaluate risk factors for GI adverse events (AEs) within a phase III trial of bevacizumab in first-line ovarian cancer therapy.
  
  
  METHODS
  Women with previously untreated advanced disease after surgery were randomly allocated to six cycles of platinum-taxane chemotherapy plus placebo cycles (C)2 to C22 (R1); chemotherapy plus bevacizumab C2 to C6 plus placebo C7 to C22 (R2); or chemotherapy plus bevacizumab C2 to C22 (R3). Patients were evaluated for history or on-study development of potential risk factors for GI AEs defined as grade ≥ 2 perforation, fistula, necrosis, or hemorrhage.
  
  
  RESULTS
  Of 1,873 patients enrolled, 1,759 (94%) were evaluable, and 2.8% (50 of 1,759) experienced a GI AE: 10 of 587 (1.7%, R1), 20 of 587 (3.4%, R2), and 20 of 585 (3.4%, R3). Univariable analyses indicated that previous treatment of inflammatory bowel disease (IBD; P = .005) and small bowel resection (SBR; P = .032) or large bowel resection (LBR; P = .012) at primary surgery were significantly associated with a GI AE. The multivariable estimated relative odds of a GI AE were 13.4 (95% CI, 3.44 to 52.3; P < .001) for IBD; 2.05 (95% CI, 1.09 to 3.88; P = .026) for LBR; 1.95 (95% CI, 0.894 to 4.25; P = .093) for SBR; and 2.15 for bevacizumab exposure (aggregated 95% CI, 1.05 to 4.40; P = .036).
  
  
  CONCLUSIONS
  History of treatment for IBD, and bowel resection at primary surgery, increase the odds of GI AEs 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 GI AE, but is not appreciably increased by continuation beyond chemotherapy.
authors.affiliation: Robert A. Burger, Fox Chase Cancer Center, Philadelphia, PA; Mark F. Brady, GOG Statistical and Data Center, Buffalo, NY; Michael A. Bookman, Arizona Cancer Center, Tucson, AZ; Bradley J. Monk, University of California at Irvine, Orange, CA; Joan L. Walker, University of Oklahoma, Oklahoma City, OK; Howard D. Homesley, Wake Forest University Medical Center, Winston-Salem, NC; Jeffrey Fowler, Ohio State University, Columbus, OH; Benjamin E. Greer, University of Washington Medical Center, Seattle, WA; Matthew Boente, Minnesota Oncology Hematology, Minneapolis, MN; Gini F. Fleming, University of Chicago, Chicago, IL; Peter C. Lim, Center of Hope at Renown Regional Medical Center, Reno, NV; Stephen C. Rubin, University of Pennsylvania Cancer Center, Philadelphia, PA; Noriyuki Katsumata, Saitama Medical University/International Medical Center-GOG Japan, Saitama, Japan; and Sharon X. Liang, North Shore University Hospital, Manhasset, NY.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Burger
authors.forename: Mark F
authors.initials: MF
authors.lastname: Brady
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bookman
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
authors.forename: Joan L
authors.initials: JL
authors.lastname: Walker
authors.forename: Howard D
authors.initials: HD
authors.lastname: Homesley
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Fowler
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Greer
authors.forename: Matthew
authors.initials: M
authors.lastname: Boente
authors.forename: Gini F
authors.initials: GF
authors.lastname: Fleming
authors.forename: Peter C
authors.initials: PC
authors.lastname: Lim
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Rubin
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Katsumata
authors.forename: Sharon X
authors.initials: SX
authors.lastname: Liang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D000068258:Bevacizumab; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000188:drug therapy; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012307:Risk Factors; D043823:Taxoids / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D043823:Taxoids; D000068258:Bevacizumab