Cetuximab and panitumumab in KRAS wild-type colorectal cancer: a meta-analysis

Int J Colorectal Dis. 2011 Jul;26(7):823-33. doi: 10.1007/s00384-011-1149-0. Epub 2011 Feb 1.

Abstract

Background: Anti-epidermal growth factor receptor monoclonal antibodies (panitumumab [P] and cetuximab [C]) are approved and effective only in KRAS wild-type patients with advanced colorectal cancer. The purpose of our meta-analysis is to evaluate the real effects of C and P in KRAS wild-type patients treated in randomized trials.

Patients and methods: Eligible studies included prospective, randomized, and controlled trials in which either C or P had been added to standard antineoplastic therapy or best supportive care and data for KRAS wild-type patients only had been calculated. Six thousand three hundred ninety-five patients' tumor samples have been analyzed (total wild-type n = 3,254; experimental arm n = 1,608; control arm n = 1,646). Relative risks (RRs) with 95% confidence intervals (CIs) for response rate were calculated, as well as hazard ratios (HRs)for progression-free survival (PFS) and overall survival.

Results: The overall RR of response rate is 1.69 (p = 0.003) in all trials. The overall HRs for PFS and survival are 0.65 (p = 0.0006) and 0.84 (p = 0.03), respectively, and both are significant. The HRs for PFS and survival in C trials are 0.64 and 0.79, respectively, and 0.65 and 0.87, respectively, in P trials, although only the results achieved in P trials are significant (p = 0.0007 and p = 0.03). Both response rate (RR = 10.94) and PFS (HR = 0.51) have increased more in pretreated patients than in first-line trials.

Conclusion: The addition of anti-EGFR monoclonal antibodies to standard anticancer therapy in KRAS wild-type colorectal cancer showed an overall significantly increased risk of objective response rate and increased progression-free and overall survival. Only the results achieved in P randomized trials are significant, and the strongest results have been achieved in pretreated patients.

Publication types

  • Meta-Analysis

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Cetuximab
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics*
  • Disease-Free Survival
  • Female
  • Humans
  • Male
  • Middle Aged
  • Panitumumab
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • ras Proteins / genetics*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Panitumumab
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Cetuximab