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

M. Macerelli, C. Caramella, L. Faivre, B. Besse, D. Planchard, V. Polo, M. Ngo Camus, A. Celebic, V. Koubi-Pick, L. Lacroix, J. P. Pignon, J. C. Soria

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)383-388
Number of pages6
JournalLung Cancer
Volume83
Issue number3
DOIs
Publication statusPublished - Mar 2014

Keywords

  • Advanced non-small cell lung cancer
  • Chemoresistance
  • KRAS
  • Platinum-based chemotherapy
  • Specific point mutations
  • Tumor aggressiveness

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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  • Cite this

    Macerelli, M., Caramella, C., Faivre, L., Besse, B., Planchard, D., Polo, V., Ngo Camus, M., Celebic, A., Koubi-Pick, V., Lacroix, L., Pignon, J. P., & Soria, J. C. (2014). Does KRAS mutational status predict chemoresistance in advanced non-small cell lung cancer (NSCLC)? Lung Cancer, 83(3), 383-388. https://doi.org/10.1016/j.lungcan.2013.12.013