title: Efficacy and safety of bevacizumab in metastatic colorectal cancer: pooled analysis from seven randomized controlled trials.
abstract: OBJECTIVE
  his analysis pooled individual patient data from randomized controlled trials (RCTs) to more thoroughly examine clinical outcomes when adding bevacizumab to chemotherapy for patients with metastatic colorectal cancer (mCRC).
  
  
  METHODS
  Patient data were pooled from the first-line AVF2107, NO16966, ARTIST, AVF0780, AVF2192, and AGITG MAX RCTs and the second-line E3200 RCT. All analyses were based on the intent-to-treat population. To assess differences in time-to-event variables by treatment (chemotherapy with or without placebo vs. chemotherapy plus bevacizumab), stratified random-effects (overall) and fixed-effects (subgroup comparisons) models were used to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs).
  
  
  RESULTS
  The analysis population comprised 3,763 patients (1,773 chemotherapy with or without placebo; 1,990 chemotherapy plus bevacizumab). The addition of bevacizumab to chemotherapy was associated with statistically significant increases in overall survival (OS; HR, 0.80; 95% CI, 0.71-0.90) and progression-free survival (PFS; HR, 0.57; 95% CI, 0.46-0.71). The effects on OS and PFS across subgroups defined by chemotherapy backbone (oxaliplatin-based, irinotecan-based), extent of disease (liver metastases only, extensive disease), age (<65, ≥65 years), Eastern Cooperative Oncology Group performance status (0, ≥1), and KRAS status (wild-type, mutant) were consistent with the overall analysis. Incidence rates of grade ≥3 hypertension, proteinuria, bleeding, wound-healing complications, gastrointestinal perforations, and thromboembolic events were increased with bevacizumab treatment.
  
  
  CONCLUSIONS
  The use of bevacizumab with chemotherapy resulted in statistically significant increases in OS and PFS for patients with mCRC. The PFS benefit extended across the clinically relevant subgroups examined. The observed safety profile of bevacizumab was consistent with that reported in individual trials.
authors.affiliation: Duke University Medical Center, Division of Hematology and Oncology, Durham, North Carolina, USA;
authors.forename: Herbert I
authors.initials: HI
authors.lastname: Hurwitz
authors.forename: Niall C
authors.initials: NC
authors.lastname: Tebbutt
authors.forename: Fairooz
authors.initials: F
authors.lastname: Kabbinavar
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Giantonio
authors.forename: Zhong-Zhen
authors.initials: ZZ
authors.lastname: Guan
authors.forename: Lada
authors.initials: L
authors.lastname: Mitchell
authors.forename: Daniel
authors.initials: D
authors.lastname: Waterkamp
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects*; D000068258:Bevacizumab; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab
keywords: Angiogenesis inhibitors; Antibodies, monoclonal, humanized; Bevacizumab; Colorectal neoplasms