KRAS as prognostic biomarker in metastatic colorectal cancer patients treated with bevacizumab: a pooled analysis of 12 published trials

Med Oncol. 2013;30(3):650. doi: 10.1007/s12032-013-0650-4. Epub 2013 Jul 5.

Abstract

The significance of KRAS in advanced colorectal cancer (CRC) treated with bevacizumab (B) is not well understood. We conducted a systematic review and pooled analysis of published trials with the aim to assess the predictive and prognostic role of KRAS status in patients treated with B. We performed a systematic search of PubMed, EMBASE, Web of Science, and Cochrane Register of Controlled Trials. The primary endpoints included objective response rate (RR), progression-free survival (PFS), and overall survival (OS). The odds ratio (OR) for RR and hazard ratios (HRs) were calculated or extracted by published data either using a fixed effect model or a random effect model. A total of 12 studies were included. A total of 2,266 patients were analysed (54 % were KRAS wt). The pooled RRs for KRAS wild-type (wt) versus mutated (mut) patients were 54.8 and 48.3 %, respectively (OR 1.42, P = 0.02). Median PFS was significantly longer in KRAS wt patients compared with that in KRAS mut patients (HR = 0.85; 95 % confidence interval (CI) 0.74-0.98; P = 0.02). Similarly, median OS was significantly better in wt KRAS patients compared with that in mut KRAS patients (HR = 0.65; 95 % CI 0.46-0.92; P = 0.01). This pooled analysis of 12 published studies shows that KRAS wt status is a good prognostic factor for B-based chemotherapy. Also, KRAS wt CRC is associated with a better RR with B plus chemotherapy than mut counterpart.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Bevacizumab
  • Biomarkers, Tumor / genetics*
  • Clinical Trials as Topic
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Disease-Free Survival
  • Humans
  • Meta-Analysis as Topic
  • Mutation / genetics
  • Prognosis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins / genetics*

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Bevacizumab
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins