2023 World Conference on Lung Cancer (Posters)-P1.22. Prevalence of KRAS Subtype Alterations in Non-Small Cell Lung Cancer (NSCLC) with Brain Metastases

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This study focuses on the prevalence of KRAS alterations and co-mutations among NSCLC (non-small cell lung cancer) brain metastases. The most common KRAS alteration observed was KRAS p.G12C, and co-mutations were found in TP53, LRP1B, STK11, KEAP1, and CDKN2A. The study suggests that co-alterations with STK11/KEAP1 are associated with worse outcomes, indicating potential therapeutic implications. It is recommended that further drug development for KRAS inhibitors with CNS (central nervous system) activity is warranted.<br /><br />The study utilized Tempus Lens, which aggregates de-identified data from samples tested with the Tempus Database, allowing real-time cohort identification and analysis. Both liquid and solid tissue biopsy data were included in the study. The Tempus xT assay detected single-nucleotide variants, copy number variants, and chromosomal rearrangements in specific genes, while the Tempus xF assay focused on single-nucleotide variants, copy number variants, and chromosomal rearrangements in different genes.<br /><br />KRAS alterations in NSCLC account for a significant percentage of lung adenocarcinomas, with a subset of these patients developing brain metastases. However, the effect of KRAS alterations on overall survival in patients with early-stage NSCLC is limited and their impact on prognosis is largely unknown. Few studies have examined the prevalence of brain metastases within each KRAS subtype. The current study aimed to fill this knowledge gap by determining the prevalence of KRAS alterations in NSCLC patients with brain metastases.<br /><br />The results showed that KRAS alterations were identified in approximately 29% of patients with brain metastasis linked to NSCLC. Among the KRAS subtypes, KRAS p.G12C was the most prevalent alteration, followed by other subtypes like G12A, G12D, G12V, and G13C. The study also analyzed immunological markers and germline landscape, and the data revealed the prevalence of certain mutations and variants associated with these markers.<br /><br />Overall, this study provides valuable insights into the prevalence of KRAS alterations and co-mutations in NSCLC brain metastases. It highlights the need for further research and drug development to improve therapeutic options for patients with these specific alterations.

Asset Subtitle

Faran Polani

Meta Tag

Speaker Faran Polani

Topic Pathology & Biomarkers: Genetic Biomarkers

Keywords

KRAS alterations

NSCLC brain metastases

KRAS p.G12C

co-mutations

worse outcomes

therapeutic implications

Tempus Lens

lung adenocarcinomas

overall survival

therapeutic options