KRAS mutation is a weak, but valid predictor for poor prognosis and treatment outcomes in NSCLC: A meta-analysis of 41 studies.

Wei Pan,Xinchen Sun,Hongcheng Zhu,Youcheng Zhang,Rongping Zhou,Yan Yang

doi:10.18632/oncotarget.7080

Wei Pan, Xinchen Sun + Show 4 more

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https://doi.org/10.18632/oncotarget.7080

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Abstract

Mutation of oncogene KRAS is common in non-small cell lung cancer (NSCLC), however, its clinical significance is still controversial. Independent studies evaluating its prognostic and predictive value usually drew inconsistent conclusions. Hence, We performed a meta-analysis with 41 relative publications, retrieved from multi-databases, to reconcile these controversial results and to give an overall impression of KRAS mutation in NSCLC. According to our findings, KRAS mutation was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in early stage resected NSCLC (hazard ratio or HR=1.56 and 1.57, 95% CI 1.39-1.76 and 1.17-2.09 respectively), and with inferior outcomes of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) treatment and chemotherapy (relative risk or RR=0.21 and 0.66 for objective response rate or ORR, 95% CI 0.12-0.39 and 0.54-0.81 respectively; HR=1.46 and 1.30 for progression-free survival or PFS, 95%CI 1.23-1.74 and 1.14-1.50 respectively) in advanced NSCLC. When EGFR mutant patients were excluded, KRAS mutation was still significantly associated with worse OS and PFS of EGFR-TKIs (HR=1.40 and 1.35, 95 % CI 1.21-1.61 and 1.11-1.64). Although KRAS mutant patients presented worse DFS and PFS of chemotherapy (HR=1.33 and 1.11, 95% CI 0.97-1.84 and 0.95-1.30), and lower response rate to EGFR-TKIs or chemotherapy (RR=0.55 and 0.88, 95 % CI 0.27-1.11 and 0.76-1.02), statistical differences were not met. In conclusion, KRAS mutation is a weak, but valid predictor for poor prognosis and treatment outcomes in NSCLC. There's a need for developing target therapies for KRAS mutant lung cancer and other tumors.

Highlights

Lung cancer, with non-small cell lung cancer (NSCLC) accounts for 85% of all cases, is the most common human malignant disease and the leading cause of cancer-related mortality worldwide [1, 2]
As the beginning of this century, novel molecular targeted agents like EGFR-TKIs represented by gefitinib or erlotinib, which interfere with EGFR signaling, have been proved dramatically effective for selected advanced NSCLC patients with sensitive EGFR mutations [3]
All of the studies focused on NSCLC or lung adenocarcinoma only except one [46] on lung squamous cell carcinoma

Summary

Introduction

With NSCLC accounts for 85% of all cases, is the most common human malignant disease and the leading cause of cancer-related mortality worldwide [1, 2]. As the beginning of this century, novel molecular targeted agents like EGFR-TKIs represented by gefitinib or erlotinib, which interfere with EGFR signaling, have been proved dramatically effective for selected advanced NSCLC patients with sensitive EGFR mutations [3]. Besides EGFR, KRAS is the most frequently mutated oncogene in NSCLC (15-20%) with most cases affect exon 2 and 3 (G12, G13 and Q61). It seemed that KRAS mutation occurs more frequently in lung adenocarcinomas (approximately 30%), in the Caucasian population, and in the population with smoking history [4,5,6]

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