The Prognostic Effect of KRAS Mutations in Non-Small Cell Lung Carcinoma Revisited: A Norwegian Multicentre Study

Abstract

Background: due to emerging therapeutics targeting KRAS G12C and previous reports with conflicting results regarding the prognostic impact of KRAS and KRAS G12C in non-small cell lung cancer (NSCLC), we aimed to investigate the frequency of KRAS mutations and their associations with clinical characteristics and outcome. Since mutation subtypes have different preferences for downstream pathways, we also aimed to investigate whether there were differences in outcome according to mutation preference for the Raf, PI3K/Akt, or RalGDS/Ral pathways. Methods: retrospectively, clinicopathological data from 1233 stage I–IV non-squamous NSCLC patients with known KRAS status were reviewed. KRAS’ associations with clinical characteristics were analysed. Progression free survival (PFS) and overall survival (OS) were assessed for the following groups: KRAS wild type (wt) versus mutated, KRAS wt versus KRAS G12C versus KRAS non-G12C, among KRAS mutation subtypes and among mutation subtypes grouped according to preference for downstream pathways. Results: a total of 1117 patients were included; 38% had KRAS mutated tumours, 17% had G12C. Among KRAS mutated, G12C was the most frequent mutation in former/current smokers (45%) and G12D in never smokers (46%). There were no significant differences in survival according to KRAS status, G12C status, among KRAS mutation subtypes or mutation preference for downstream pathways. Conclusion: KRAS status or KRAS mutation subtype did not have any significant influence on PFS or OS.

AMG-510 and cisplatin combination increases antitumor effect in lung adenocarcinoma with mutation of KRAS G12C: a preclinical and translational research

“…A previous report suggested that among NSCLC patients, White (13.0%) and Black patients (10.9%) had more proportion of KRAS G12C mutations than Asians (3.6%) [ 27 ]. Other studies also confirmed this distribution phenomenon of KRAS G12C mutation [ 28 – 30 ]. The proportion of KRAS G12C mutation was low in the present study, like the abovementioned research.…”

Prognostic Implication of KRAS G12C Mutation in a Real-World KRAS-Mutated Stage IV NSCLC Cohort Treated With Immunotherapy in The Netherlands

“…This contrasts with two large cohorts from France and Germany 10 , 41 but corresponds with other studies. 2 , 8 , 9 , 42 In our study, sex was a significant prognostic factor for OS, as women had a better survival than men which was not explained by differences in patient and tumor characteristics ( p < 0.0001). This was not found in other larger KRAS cohorts, but in these cohorts, patients with stages I to IV NSCLC with different treatment modalities were included, 42 , 43 and our study included only those with stage IV treated with systemic therapy.…”

Associations between detectable circulating tumor DNA and tumor glucose uptake measured by 18F-FDG PET/CT in early-stage non-small cell lung cancer

“…ctDNA data was available from three previous studies [ 15 – 17 ]. In one cohort, tumor tissue DNA was screened for a pathogenic mutation in the gene Kirsten Rat Sarcoma Viral Oncogene Homolog ( KRAS ) [ 18 ]. Tumor tissue DNA in the other cohorts were screened for pathogenic mutations in 22[ 17 ] or 275[ 16 ] genes using next-generation sequencing (NGS).…”