Common and rare EGFR and KRAS mutations in a Dutch non-small-cell lung cancer population and their clinical outcome

PLoS One. 2013 Jul 29;8(7):e70346. doi: 10.1371/journal.pone.0070346. Print 2013.

Abstract

Introduction: In randomly assigned studies with EGFR TKI only a minor proportion of patients with NSCLC have genetically profiled biopsies. Guidelines provide evidence to perform EGFR and KRAS mutation analysis in non-squamous NSCLC. We explored tumor biopsy quality offered for mutation testing, different mutations distribution, and outcome with EGFR TKI.

Patient and methods: Clinical data from 8 regional hospitals were studied for patient and tumor characteristics, treatment and overall survival. Biopsies sent to the central laboratory were evaluated for DNA quality and subsequently analyzed for mutations in exons 18-21 of EGFR and exon 2 of KRAS by bidirectional sequence analysis.

Results: Tumors from 442 subsequent patients were analyzed. For 74 patients (17%) tumors were unsuitable for mutation analysis. Thirty-eight patients (10.9%) had EGFR mutations with 79% known activating mutations. One hundred eight patients (30%) had functional KRAS mutations. The mutation spectrum was comparable to the Cosmic database. Following treatment in the first or second line with EGFR TKI median overall survival for patients with EGFR (n = 14), KRAS (n = 14) mutations and wild type EGFR/KRAS (n = 31) was not reached, 20 and 9 months, respectively.

Conclusion: One out of every 6 tumor samples was inadequate for mutation analysis. Patients with EGFR activating mutations treated with EGFR-TKI have the longest survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Biopsy
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • ErbB Receptors / genetics*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Mutation*
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Netherlands
  • Patient Outcome Assessment
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use
  • Treatment Outcome
  • ras Proteins / genetics*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • ErbB Receptors
  • ras Proteins

Grants and funding

This work was partly funded by the CTMM Air Force consortium (http://www.ctmm.nl). CTMM pays for GSMAK's salary and had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. No other external funding sources for this study.