Resectability and outcome with anti-EGFR agents in patients with KRAS wild-type colorectal liver-limited metastases: a meta-analysis

Int J Colorectal Dis. 2012 Aug;27(8):997-1004. doi: 10.1007/s00384-012-1438-2. Epub 2012 Feb 23.

Abstract

Background: Cetuximab (C) and panitumumab (P) increase response rate and survival in KRAS wild-type metastatic colorectal cancer (mCRC). We performed a meta-analysis of randomised controlled trials (RCTs) to assess their effect on overall response rate (ORR), the rate of radical resection (R0) and survival in patients with liver-limited initially unresectable mCRC.

Materials and methods: We searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials for RCTs comparing first-line chemotherapy plus or minus C or P and reporting data in patients with KRAS wild-type, unresectable liver-limited mCRC. Relative risks (RRs) with 95% confidence interval were calculated. Meta-analysis of hazard ratios (HRs) for progression-free and overall survival (PFS and OS) was also performed.

Results: Four RCTs involving 484 KRAS wild-type patients were included. Compared to chemotherapy alone, the addition of C or P significantly increased the ORR (RR 1.67, p = 0.0001), the R0 resection rate from 11% to 18% (RR 1.59, p = 0.04) and PFS (HR 0.68, p = 0.002), but not OS (p = 0.42).

Conclusions: The addition of C and P increased the R0 resection rate by 60% and reduced the risk of progression by 32% in patients with mCRC and unresectable liver-limited disease. This combination represents one of the preferred choices as conversion therapy in KRAS wild-type patients with unresectable liver metastases.

Publication types

  • Meta-Analysis

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cetuximab
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • DNA Mutational Analysis
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / metabolism
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / surgery*
  • Panitumumab
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Publication Bias
  • Randomized Controlled Trials as Topic
  • Risk
  • Treatment Outcome
  • ras Proteins / genetics*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Panitumumab
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Cetuximab