Predictive and Prognostic Biomarkers for Patients Treated with Anti-EGFR Agents in Lung Cancer: A Systemic Review and Meta-Analysis.

Ying Wang,Qi Liu,Hong-Chang Shen,Kai Wang,Jia-Jun Du,Xiao Qu

doi:10.7314/apjcp.2015.16.11.4759

Abstract

Several studies have investigated predictive and prognostic biomarkers for patients treated with anti-epidermal growth factor receptor (EGFR) agents in lung cancer. However, the conclusion is controversial. A meta-analysis was conducted to evaluate the associations of mutant K-ras, PIK3CA and PTEN deficiency with the efficacy of anti-EGFR agents in lung cancer. The primary endpoint was objective response rate (ORR). The secondary endpoints were overall survival (OS) and progression-free survival (PFS). A total of 61 studies were included in the final meta-analysis. The result showed that K-ras mutation was a good predictor for ORR (RR=0.42, 95%CI, 0.33-0.55, p=0.000) and an effective prognostic marker for OS (HR=1.37, 95%CI, 1.15-1.65, p=0.001) and PFS (HR=1.33, 95%CI, 1.05-1.69, p=0.019). However, PTEN deficiency or PIK3CA mutation did not show any significance predictive value for ORR (PTEN, RR=0.82, 95%CI, 0.56-1.19, p=0.286; PIK3CA, RR=1.08, 95%CI, 0.17-6.66, P=0.938). And PTEN deficiency or expression of PIK3CA did not show significance prognostic value for OS (PTEN, HR=0.88, 95%CI, 0.31-2.46,P=0.805; PIK3CA, HR=0.79, 95%CI: 0.23-2.68, P=0.706). Our meta-analysis showed that K-ras mutation may be an effective predictor in lung cancer patients treated with anti-EGFR agents. Whereas, the predictive and prognostic value of PTEN deficiency and PIK3CA mutation need to be further investigated.

Highlights

Lung cancer is the leading cause of cancer-related death in both sexes worldwide (Siegel et al, 2013)
Our meta-analysis showed that K-ras mutation may be an effective predictor in lung cancer patients treated with anti-epidermal growth factor receptor (EGFR) agents
Inclusion criteria The inclusion criteria to obtain eligible studies: i) evaluating the K-ras mutations, loss of PTEN expression, PIK3CA mutations status and response to anti-EGFR agents in lung cancer; ii) sufficient data on objective response rate (ORR), overall survival (OS), progression-free survival (PFS) stratified by corresponding mutation status; iii) studies with full text articles; iv)when the same author or group reported results obtained from the same patient population in several publications, only the most recent report or most informative one was included; Studies included in our analysis are assessed by two reviewers

Summary

Introduction

Lung cancer is the leading cause of cancer-related death in both sexes worldwide (Siegel et al, 2013). Several studies have investigated predictive and prognostic biomarkers for patients treated with anti-epidermal growth factor receptor (EGFR) agents in lung cancer. Materials and Methods: A meta-analysis was conducted to evaluate the associations of mutant K-ras, PIK3CA and PTEN deficiency with the efficacy of anti-EGFR agents in lung cancer. The result showed that K-ras mutation was a good predictor for ORR (RR=0.42, 95%CI, 0.33-0.55, p=0.000) and an effective prognostic marker for OS (HR=1.37, 95%CI, 1.15-1.65, p=0.001) and PFS (HR=1.33, 95%CI, 1.05-1.69, p=0.019). PTEN deficiency or PIK3CA mutation did not show any significance predictive value for ORR (PTEN, RR=0.82, 95%CI, 0.56-1.19, p=0.286; PIK3CA, RR=1.08, 95%CI, 0.17-6.66, P=0.938). Conclusions: Our meta-analysis showed that K-ras mutation may be an effective predictor in lung cancer patients treated with anti-EGFR agents. The predictive and prognostic value of PTEN deficiency and PIK3CA mutation need to be further investigated

Methods

Results

Conclusion