| Summary: | Background: due to emerging therapeutics targeting <i>KRAS</i> G12C and previous reports with conflicting results regarding the prognostic impact of <i>KRAS</i> and <i>KRAS</i> G12C in non-small cell lung cancer (NSCLC), we aimed to investigate the frequency of <i>KRAS</i> 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 <i>KRAS</i> status were reviewed. <i>KRAS</i>’ associations with clinical characteristics were analysed. Progression free survival (PFS) and overall survival (OS) were assessed for the following groups: <i>KRAS</i> wild type (wt) versus mutated, <i>KRAS</i> wt versus <i>KRAS</i> G12C versus <i>KRAS</i> non-G12C, among <i>KRAS</i> mutation subtypes and among mutation subtypes grouped according to preference for downstream pathways. Results: a total of 1117 patients were included; 38% had <i>KRAS</i> mutated tumours, 17% had G12C. Among <i>KRAS</i> 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 <i>KRAS</i> status, G12C status, among <i>KRAS</i> mutation subtypes or mutation preference for downstream pathways. Conclusion: <i>KRAS</i> status or <i>KRAS</i> mutation subtype did not have any significant influence on PFS or OS.
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