Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Mutation Testing Trends, Prevalence, and Outcomes in Metastatic, Non-Squamous Non-Small Cell Lung Cancer (Non-SQ NSCLC) Patients in Queensland, Australia From 2014-2023.

[BACKGROUND] Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most commonly mutated oncogene in solid tumors, detected in up to 30% of lung adenocarcinomas. This study aimed to address gaps in the literature by analyzing KRAS mutations (KRASM) in a large Australian population.

[METHODS] A total of 3982 patients with metastatic nonsquamous nonsmall cell lung cancer diagnosed via public hospitals were retrospectively analyzed from January 1, 2014 to December 31, 2023. Records were reviewed for evidence of KRASM testing, KRAS results, biopsy type, and programmed death-ligand 1 (PD-L1) status. KRASM testing rates were also compared to that of other commonly tested oncogenic mutations.

[RESULTS] KRASM testing was performed in 52.9% of eligible patients, improving from 1.9% in 2014 to 86.3% in 2023. KRASM was identified in 830 patients (39.4% of KRASM tested patients, 20.8% overall). The most common KRASM seen was 12th codon substitution of KRAS glycine to cysteine (G12C) followed by substitutions of glycine to valine (G12V) and glycine to aspartate (G12D). Patients harboring KRASM were significantly more likely to have smoked, be female, and have higher PD-L1 expression than their KRAS wild type (wt) counterparts. All-cause survival was higher at the 1-year (43.9% vs. 35.3%) and 5-year (12.4% vs. 8.9%) marks in KRAS wt patients compared to KRAS mt.

[CONCLUSION] This study is the largest longitudinal analysis of KRASM testing conducted in Australia, with significant improvement in testing rates seen over the time period. Rates of KRASM and characteristics of Australian KRAS mt patients correspond with published literature.