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

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.

Circulating cell-free DNA as a prognostic and predictive biomarker in non-small cell lung cancer

“…Many studies reported that KRAS mutation could predict the poor outcomes of EGFR-TKIs treatment and chemotherapy, but several studies argued that KRAS mutation was not associated with the outcome of NSCLC patients [54]. A meta-analysis aimed to clarify the prognostic and predictive value of KRAS mutation in NSCLC was carried out recently [54]. Its results showed that KRAS mutation was significantly associated with worse OS and disease-free survival (DFS) in early stage NSCLC, and with inferior outcomes of EGFR-TKIs treatment and chemotherapy.…”

Analysis of the clinicopathologic characteristics and prognostic of stage I invasive mucinous adenocarcinoma

“…In general, invasive mucinous adenocarcinoma had a correlation with KRAS mutation, whereas nonmucinous adenocarcinomas have a low KRAS mutation rate but a frequent EGFR mutation. However, the value of KRAS mutation in predicting prognosis of early stage IMA patients still need further study (Marabese et al 2015;Pan et al 2016).…”

KRAS mutations in the circulating free DNA (cfDNA) of non-small cell lung cancer (NSCLC) patients

“…In relation to NSCLC, KRAS mutations were shown to be significantly associated with inferior outcomes to chemotherapy and EGFR-TKIs (14). However, when EGFR mutant patients were excluded, there were no statistical differences between progression-free survival (PFS) to chemotherapy and response rates to EGFR-TKIs or chemotherapy.…”

“…KRAS mutations: prognostic and predictive value of cfDNA in NSCLC As mentioned, KRAS mutations in tissue could be a weak, but valid, predictor of poor prognosis and treatment outcome (14). Therefore, several studies have tried to uncover the same kind of correlation between the presence of KRAS mutations in blood and clinical outcome in order to use KRAS as a biomarker.…”