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

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 PIK3 CA 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 PIK3 CA 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. PIK3 CA mutation showed similar trends. In addition to EGFR, adding K-ras and PIK3 CA 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.

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 （OK =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 EGFR- TKIs. 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.