Clinical presentation and outcomes according to KRAS status in advanced non-small cell lung cancer

Abstract

The goal of the current study was to assess the frequency of KRAS mutation subtypes in a cohort of advanced non-small cell lung cancer (NSCLC). More importantly, we present the clinical characteristics, treatment profile, as well as overall survival (OS) according to KRAS mutational status . This study comprised a retrospective analysis of patients from a cancer center database from 2016 to 2019. All patients had confirmed diagnosis of non-squamous NSCLC by pathological examination (histology or cytology), metastatic disease ( de novo or recurrence) and were tested for KRAS mutations. A total of 200 patients were included; 25 had G12C (12.5%), 33 had KRAS non-G12C mutations (16.5%), and 142 were wild type (71.0%). Mean age at diagnosis was 63.9 years (SD 11.0); most patients were females (60.5%), smokers (70.0%), and were diagnosed with advanced disease (13.1% and 80.8% at stages III and IV, respectively). Adenocarcinoma comprised 99% of tumors, and 19.5% presented central nervous system (CNS) involvement. CNS was more often involved in KRAS G12C-mutant cases ( p = 0.044), and KRAS mutations were inversely associated with EGFR ( p < 0.001). Survival was not significantly different according to KRAS status ( p = 0.41). Median OS was 10.6 months (95% CI, 8.9–15.7), 11.7 months (95% CI, 5.1–34.8), and 7.7 months (95% CI, 5.0-18.4) in KRAS wild type, G12C, and non-G12C mutants, respectively. KRAS G12C was present in relatively high frequency, and lacked prognostic impact in the current study. This mutation may develop independently of clinical factors, and therefore should be routinely tested in all patients with advanced, non-squamous NSCLC.