Does KRAS mutational status predict chemoresistance in advanced non-small cell lung cancer (NSCLC)?

Lung Cancer. 2014 Mar;83(3):383-8. doi: 10.1016/j.lungcan.2013.12.013. Epub 2014 Jan 3.


Background: Clinical implications of KRAS mutational status in advanced non-small cell lung cancer (NSCLC) remain unclear. To clarify this point, we retrospectively explored whether KRAS mutations could impact tumor response, and disease control rate (DCR) to first-line platinum-based chemotherapy (CT) as well as progression-free survival (PFS) or overall survival (OS).

Methods: Between June 2009 and June 2012, 340 patients with advanced (stage IIIB/IV) NSCLC were reviewed in a single institution (Institut Gustave Roussy). Two hundred and one patients had a biomolecular profile and received a platinum-based first-line CT. Patients with an unknown mutational status or with actionable alterations were excluded. We retained two groups: patients with KRAS mutated tumor (MUT) and patients with wild-type KRAS/EGFR (WT). Multivariate analyses with Cox model were used. Survival curves were calculated with Kaplan-Meier method.

Results: One hundred and eight patients were included in the analysis: 39 in the MUT group and 69 in the WT group. Baseline radiological assessment demonstrated more brain (P=0.01) and liver (P=0.04) metastases in MUT patients. DCR was 76% for MUT vs. 91% for WT group (P=0.03), regardless of the type of platinum-based CT (use of pemetrexed or not). Although no statistically significant differences were found, shorter PFS (4.9 vs. 6.0 months; P=0.79) and OS (10.3 vs. 13.2 months; P=0.40) were observed for patients with KRAS mutated tumors in univariate analysis.

Conclusions: KRAS mutant tumors had a lower DCR after the first-line platinum-based CT, but this difference did not translate in PFS or OS. The presence of KRAS mutations may confer a more aggressive disease, with greater baseline incidence of hepatic and cerebral metastases.

Keywords: Advanced non-small cell lung cancer; Chemoresistance; KRAS; Platinum-based chemotherapy; Specific point mutations; Tumor aggressiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinogenesis
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • DNA Mutational Analysis
  • Drug Resistance, Neoplasm / genetics
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Mutation / genetics
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Retrospective Studies
  • Survival Analysis
  • Tumor Burden / drug effects
  • ras Proteins / genetics*


  • KRAS protein, human
  • Proto-Oncogene Proteins
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins