Predictive value of K-ras and PIK3CA in non-small cell lung cancer patients treated with EGFR-TKIs: a systemic review and meta-analysis

<b>Objective:</b>A meta-analysis was performed to augment the insufficient data on the impact of mutative <i>EGFR</i> downstream phosphatidylinositol-3-kinase (<i>PI3K</i>) and mitogen-activated protein kinase (<i>MAPK</i>) pathways on the clinical efficiency of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment of non-small cell lung cancer (NSCLC) patients.<br/><b>Methods:</b>Network databases were explored in April, 2015. Papers that investigated the clinical outcomes of NSCLC patients treated with <i>EGFR</i>-TKIs according to the status of <i>K-ras</i> and/or <i>PIK3CA</i> gene mutation were included. A quantitative meta-analysis was conducted using standard statistical methods. Odds ratios (ORs) for objective response rate (ORR) and hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were calculated.<br/><b>Results:</b>Mutation in <i>K-ras</i> significantly predicted poor ORR[OR=0.22; 95% confidence interval (CI), 0.13-0.35], shorter PFS (HR=1.56; 95% CI, 1.27-1.92), and shorter OS (HR=1.59; 95% CI, 1.33-1.91) in NSCLC patients treated with <i>EGFR</i>-TKIs. Mutant PIK3CA significantly predicted shorter OS (HR=1.83; 95% CI, 1.05-3.20), showed poor ORR (OR=0.70; 95% CI, 0.22-2.18), and shorter PFS (HR=1.79; 95% CI, 0.91-3.53) in NSCLC patients treated with EGFR-TKIs.<br/><b>Conclusion:</b><i>K-ras</i> mutation adversely affected the clinical response and survival of NSCLC patients treated with EGFRTKIs. <i>PIK3CA</i> mutation showed similar trends. In addition to EGFR, adding <i>K-ras</i> and <i>PIK3CA</i> as routine gene biomarkers in clinical genetic analysis is valuable to optimize the effectiveness of EGFR-TKI regimens and identify optimal patients who will benefit from <i>EGFR</i>-TKI treatment.

Abstract licence: CC BY-NC

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