Detection of K-ras Mutations in Predicting Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase (EGFR-TK) Inhibitor in Patients with Metastatic Colorectal Cancer

PLoS One. 2015 May 7;10(5):e0101019. doi: 10.1371/journal.pone.0101019. eCollection 2015.

Abstract

Epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors are useful in treating different advanced human cancers; however, their clinical efficacy varies. This study detected K-ras mutations to predict the efficacy of EGFR-TK inhibitor cetuximab treatment on Chinese patients with metastatic colorectal cancer (mCRC). A total of 87 patients with metastatic colorectal cancer were treated with cetuximab for 2-16 months, in combination with chemotherapy between August 2008 and July 2012, and tissue samples were used to detect K-ras mutations. The data showed that K-ras mutation occurred in 27/87 (31%). The objective response rates and disease control rate in K-ras wild type and mutant patients were 42% (25/60) versus 11% (3/27) (p<0.05) and 60% (36/60) versus 26% (7/27) (p<0.05), respectively. Patients with the wild-type K-ras had significantly higher median survival times and progression-free survival, than patients with mutated K-ras (21 months versus 17 months, p=0.017; 10 months versus 6 months, p=0.6). These findings suggest that a high frequency of K-ras mutations occurs in Chinese mCRC patients and that K-ras mutation is required to select patients for eligibility for cetuximab therapy. Further prospective studies using a large sample size are needed to confirm these preliminary findings.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Asians / genetics*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Cetuximab / administration & dosage*
  • China
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Female
  • Humans
  • Irinotecan
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Metastasis
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • KRAS protein, human
  • Organoplatinum Compounds
  • Oxaliplatin
  • Irinotecan
  • Proto-Oncogene Proteins p21(ras)
  • Cetuximab
  • Camptothecin

Grant support

The authors have no support or funding to report.