title: Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of bevacizumab when added to first-line oxaliplatin-based chemotherapy (either capecitabine plus oxaliplatin [XELOX] or fluorouracil/folinic acid plus oxaliplatin [FOLFOX-4]) in patients with metastatic colorectal cancer (MCRC).
  
  
  METHODS
  Patients with MCRC were randomly assigned, in a 2 x 2 factorial design, to XELOX versus FOLFOX-4, and then to bevacizumab versus placebo. The primary end point was progression-free survival (PFS).
  
  
  RESULTS
  A total of 1,401 patients were randomly assigned in this 2 x 2 analysis. Median progression-free survival (PFS) was 9.4 months in the bevacizumab group and 8.0 months in the placebo group (hazard ratio [HR], 0.83; 97.5% CI, 0.72 to 0.95; P = .0023). Median overall survival was 21.3 months in the bevacizumab group and 19.9 months in the placebo group (HR, 0.89; 97.5% CI, 0.76 to 1.03; P = .077). Response rates were similar in both arms. Analysis of treatment withdrawals showed that, despite protocol allowance of treatment continuation until disease progression, only 29% and 47% of bevacizumab and placebo recipients, respectively, were treated until progression. The toxicity profile of bevacizumab was consistent with that documented in previous trials.
  
  
  CONCLUSIONS
  The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved PFS in this first-line trial in patients with MCRC. Overall survival differences did not reach statistical significance, and response rate was not improved by the addition of bevacizumab. Treatment continuation until disease progression may be necessary in order to optimize the contribution of bevacizumab to therapy.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-917, New York, NY 10021, USA. saltzl@mskcc.org
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Saltz
authors.forename: Stephen
authors.initials: S
authors.lastname: Clarke
authors.forename: Eduardo
authors.initials: E
authors.lastname: Díaz-Rubio
authors.forename: Werner
authors.initials: W
authors.lastname: Scheithauer
authors.forename: Arie
authors.initials: A
authors.lastname: Figer
authors.forename: Ralph
authors.initials: R
authors.lastname: Wong
authors.forename: Sheryl
authors.initials: S
authors.lastname: Koski
authors.forename: Mikhail
authors.initials: M
authors.lastname: Lichinitser
authors.forename: Tsai-Shen
authors.initials: TS
authors.lastname: Yang
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivera
authors.forename: Felix
authors.initials: F
authors.lastname: Couture
authors.forename: Florin
authors.initials: F
authors.lastname: Sirzén
authors.forename: Jim
authors.initials: J
authors.lastname: Cassidy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010919:Placebos
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D010919:Placebos; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil