Impact of specific mutant KRAS on clinical outcome of EGFR-TKI-treated advanced non-small cell lung cancer patients with an EGFR wild type genotype

Giulio Metro, Rita Chiari, Simona Duranti, Annamaria Siggillino, Matthias J. Fischer, Diana Giannarelli, Vienna Ludovini, Chiara Bennati, Luca Marcomigni, Alice Baldi, Michele Giansanti, Vincenzo Minotti, Lucio Crinò

Research output: Contribution to journalArticle

Abstract

Introduction: This retrospective study was undertaken to investigate the impact of specific mutant KRAS on clinical outcome to either gefitinib or erlotinib (EGFR tyrosine kinase inhibitor, EGFR-TKI) in patients with EGFR wild type (WT) advanced non-small cell lung cancer (NSCLC). Methods: Patients with an EGFR WT genotype who were treated with an EGFR-TKI for advanced disease at our Institution were identified. Simultaneous availability of KRAS mutation status was required for study inclusion. Results: Sixty-seven patients were eligible. Median age was 60 years (39-84), and 10 patients (14.9%) had received an EGFR-TKI as upfront therapy. Overall, the median progression-free survival (PFS) and overall survival (OS) were 2.9 months and 18.0 months, respectively. KRAS mutant patients (n= 18) experienced a significantly shorter PFS compared with those carrying a KRAS WT genotype (n= 49) (1.6 months vs 3.0 months, respectively, P= 0.04; HR = 1.92). However, within the KRAS mutant group a great variability in terms of sensitivity to treatment was noted (PFS ranging from 0.7 months to 38.7 months). KRAS codon 13 mutant patients (n= 4) experienced the worse outcome when compared with KRAS codon 12 mutants (n= 14) and KRAS WT patients (P<0.0001 and P= 0.01 for PFS and OS, respectively). Conclusions: Though we found that EGFR WT/. KRAS mutant advanced NSCLC patients are associated with an increased resistance to treatment, specific mutant KRAS may account for differential sensitivity to an EGFR-TKI. KRAS codon 13 mutants are those who seem to experience the worse clinical outcome.

Original languageEnglish
Pages (from-to)81-86
Number of pages6
JournalLung Cancer
Volume78
Issue number1
DOIs
Publication statusPublished - Oct 2012

Keywords

  • EGFR
  • EGFR-TKI
  • Erlotinib
  • Gefitinib
  • KRAS
  • Non-small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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  • Cite this

    Metro, G., Chiari, R., Duranti, S., Siggillino, A., Fischer, M. J., Giannarelli, D., Ludovini, V., Bennati, C., Marcomigni, L., Baldi, A., Giansanti, M., Minotti, V., & Crinò, L. (2012). Impact of specific mutant KRAS on clinical outcome of EGFR-TKI-treated advanced non-small cell lung cancer patients with an EGFR wild type genotype. Lung Cancer, 78(1), 81-86. https://doi.org/10.1016/j.lungcan.2012.06.005