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

Abstract

Objective:A meta-analysis was performed to augment the insufficient data on the impact of mutative EGFR downstream phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways on the clinical efficiency of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment of non-small cell lung cancer (NSCLC) patients.Methods:Network databases were explored in April, 2015. Papers that investigated the clinical outcomes of NSCLC patients treated with EGFR-TKIs according to the status of K-ras and/or PIK3CA 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.Results:Mutation in K-ras 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 EGFR-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.Conclusion:K-ras mutation adversely affected the clinical response and survival of NSCLC patients treated with EGFRTKIs. PIK3CA mutation showed similar trends. In addition to EGFR, adding K-ras and PIK3CA 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 EGFR-TKI treatment.

Keywords

• Non-small cell lung cancer (NSCLC)
• tyrosine kinase inhibitor (TKI)
• targeted therapy
• <i>K-ras</i>
• <i>PIK3CA</i>
• meta-analysis