Prognostic value of EGFR and KRAS in circulating tumor DNA in patients with advanced non-small cell lung cancer: a systematic review and meta-analysis.

Kuo Zhang,Jiansheng Ding,Gaowei Fan,Jinming Li

doi:10.18632/oncotarget.15412

Kuo Zhang, Jiansheng Ding + Show 2 more

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https://doi.org/10.18632/oncotarget.15412

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Abstract

EGFR (exon 19 and exon 21) mutations in patients with advanced non-small cell lung cancer (NSCLC) treated by EGFR-TKIs are associated with a better survival; while KRAS mutations predict a worse prognosis. However, there are divergent findings regarding the prognostic value of EGFR and KRAS mutations in circulating tumor DNA (ctDNA). We aimed to summarize the evidence for the use of circulating EGFR and KRAS mutations as prognostic factors in advanced NSCLC patients.We searched the network databases for studies reporting progression-free survival (PFS) and overall survival (OS) stratified by EGFR or KRAS mutations in ctDNA in advanced NSCLC patients. Thirteen studies enrolling 2,293 patients were reviewed. Correlation of circulating EGFR or KRAS mutations with patients’ prognosis was assessed by meta-analysis.The pooled analyses showed that EGFR mutations in ctDNA significantly prolong PFS (HR=0.64,95% CI 0.51-0.81, I2=0%, p=0.0002), namely, in patients treated by EGFR-TKIs. There is a trend to have a prolonged OS for advanced NSCLC patients with circulating EGFR mutations who were treated by EGFR-TKIs (HR=0.79, 95% CI 0.52-1.21, I2=0, p=0.28). KRAS mutations detected in ctDNA predict a worse PFS (HR=1.83, 95% CI 1.40-2.40, p<0.0001) and OS (HR=2.07, 95% CI 1.54-2.78, p<0.00001) in advanced NSCLC patients treated by chemotherapy. Sensitivity analyses and subgroup analyses demonstrated the stability of our conclusion.Our analysis showed that EGFR mutations in ctDNA predicted a better PFS, in particular in advanced NSCLC patients treated by EGFR-TKIs. KRAS mutations in ctDNA indicated a worse PFS and OS in patients treated by chemotherapy.

Highlights

Non-small cell lung cancer (NSCLC) remains the major cause of cancer-related mortality
Our analysis showed that epidermal growth factor receptor (EGFR) mutations in circulating tumor DNA (ctDNA) predicted a better progression-free survival (PFS), in particular in advanced NSCLC patients treated by EGFR-tyrosine kinase inhibitors (TKIs)
Of the remaining 79 studies, the full text was screened and 66 studies were excluded for lack of follow-up, no information about prognosis, not restricted to advanced NSCLC patients, non-English literature, not restricted to KRAS or EGFR mutations

Summary

Introduction

Non-small cell lung cancer (NSCLC) remains the major cause of cancer-related mortality. Studies showed that epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) confer better outcome in patients with EGFR mutations (exon 19 deletions, exon 21 L858R point mutations) than in those with the wild type [1]. About 5-15% of NSCLC patients harbor EGFR mutations [2]. KRAS mutations predict worse prognosis among NSCLC patients treated by EGFR-TKIs or chemotherapy [3, 4]. KRAS mutations are detected in about 30% of NSCLC in white people [5]. 97% of KRAS mutations in NSCLC involve codon 12 or codon 13 [3, 6]. Several studies performed systematic review and metaanalysis to assess the prognostic value of EGFR and KRAS mutations in tumor tissue in NSCLC patients [4, 7,8,9]

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