KRAS mutations affect prognosis of non-small-cell lung cancer patients treated with first-line platinum containing chemotherapy

Oncotarget. 2015 Oct 20;6(32):34014-22. doi: 10.18632/oncotarget.5607.

Abstract

KRAS mutations seem to indicate a poor outcome in Non-Small-Cell Lung Cancer (NSCLC) but such evidence is still debated. The aim of this planned ancillary study within the TAILOR trial was to assess the prognostic value of KRAS mutations in advanced NSCLC patients treated with platinum-based first-line chemotherapy. Patients (N = 540), enrolled in the study in 52 Italian hospitals, were centrally genotyped twice in two independent laboratories for EGFR and KRAS mutational status.Of these, 247 patients were eligible and included in the present study. The primary endpoint was overall survival (OS) according to KRAS mutational status in patients harboring EGFR wild-type.Sixty (24.3%) out of 247 patients harbored KRAS mutations. Median OS was 14.3 months and 10.6 months in wild-type and mutated KRAS patients, respectively (unadjusted Hazard Ratio [HR]=1.41, 95%Confidence Interval [CI]: 1.03-1.94 P = 0.032; adjusted HR=1.39, 95%CI: 1.00-1.94 P = 0.050). This study, with all consecutive patients genotyped, indicates that the presence of KRAS mutations has a mild negative impact on OS in advanced NSCLC patient treated with a first-line platinum-containing regimen.

Trial registration: clinicaltrials.gov identifierNCT00637910.

Keywords: KRAS; NSCLC; first-line; platinum.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • DNA Mutational Analysis
  • Disease-Free Survival
  • ErbB Receptors / genetics
  • Female
  • Genotype
  • Humans
  • Italy
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Mutation
  • Platinum / therapeutic use*
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Treatment Outcome

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00637910