KRAS Mutation in Patients with Lung Cancer: A Predictor for Poor Prognosis but Not for EGFR-TKIs or Chemotherapy
- 1.2k Downloads
The prognostic and predictive value of KRAS mutations in patients with lung cancer is controversial. Biases in disease stage, treatment regimen, small-scale patient studies, and biomarker status have led to inconsistent results in previous reports.
The KRAS and EGFR genes were examined in 1935 consecutive patients with non-small cell lung cancer. All patients were divided into KRAS mutation (KRAS group), EGFR mutation (EGFR group), and KRAS/EGFR wild type (WT group) groups. Randomly selected cases were paired with patients with the KRAS mutation, the EGFR mutation, and KRAS/EGFR wild type patients according to tumor, node, metastasis stage, time of first visit within 1 year, and pathology. Progression-free survival (PFS) and overall survival were evaluated by Kaplan–Meier and Cox models.
The KRAS mutation rate for lung adenocarcinoma was 5.90 %. The overall survival was 14.47, 20.57, and 42.73 months for the KRAS group, WT group, and EGFR group, respectively (P < 0.001). Multivariate analysis indicated that KRAS mutation status was an independent prognostic factor (hazard ratio 2.69, 95 % confidence interval 1.91–3.80, P < 0.001). No difference was found in PFS and tumor responsiveness between patients with a KRAS mutation and those with wild type KRAS/EGFR for chemotherapy and EGFR tyrosine kinase inhibitors (TKI). PFS did not significantly differ for chemotherapy among the three groups (P = 0.270).
KRAS mutation is a poor prognosis factor, but it is not an independent predictor of response to EGFR-TKI or chemotherapy in patients with lung cancer.
KeywordsOverall Survival Epidermal Growth Factor Receptor Epidermal Growth Factor Receptor Mutation KRAS Mutation Advanced NSCLC
Supported in part by grants from the National Natural Science Foundation of China (81001031, 30871126), Industry Technology Research and Development Project of Guangdong Science and Technology Department (2011A030400010), and Guangzhou Science and Information Technology Bureau (2011Y2-00014).
None of the authors have a potential conflict of interest
- 22.Linardou H, Dahabreh IJ, Kanaloupiti D, et al. Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer. Lancet Oncol. 2008;9:962–72.PubMedCrossRefGoogle Scholar
- 24.Jackman DM, Miller VA, Cioffredi LA, et al. Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated non-small cell lung cancer patients: results of an online tumor registry of clinical trials. Clin Cancer Res. 2009;15:5267–73.PubMedCrossRefGoogle Scholar
- 27.Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.PubMedCrossRefGoogle Scholar
- 28.Kramer D, Thunnissen FB, Gallegos-Ruiz MI, et al. A fast, sensitive and accurate high resolution melting (HRM) technology-based assay to screen for common K-ras mutations. Cell Oncol. 2009;31(3):161–7.Google Scholar
- 32.Poullis M, McShane J, Shaw M, et al. Smoking status at diagnosis and histology type as determinants of long-term outcomes of lung cancer patients. Eur J Cardiothorac Surg. doi: 10.1093/ejcts/ezs464.