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

P1.22. Prevalence of KRAS Subtype Alterations in Non-Small Cell Lung Cancer (NSCLC) with Brain Metastases - PDF(Abstract)

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A study presented at the World Conference on Lung Cancer in 2023 examined the prevalence of KRAS subtype alterations in non-small cell lung cancer (NSCLC) patients with brain metastases. The study found that KRAS alterations were identified in 28.93% of NSCLC patients with brain metastases, with the most prevalent alteration being KRAS p.G12C. The study also identified co-alterations in genes such as TP53, LRP1B, STK11, KEAP1, and CDKN2A. The findings suggest that blood-based testing may be a viable diagnostic tool for detecting brain metastases with KRAS alterations. <br /><br />The study included data from both liquid and solid tissue biopsy, with a total of 4321 cases of brain metastasis linked to NSCLC identified. Among the KRAS alteration subgroup (n=1250), the most frequent KRAS alterations were p.G12C, p.G12V, p.G12D, p.G12A, and p.G13C. Additionally, co-alterations were observed in genes such as TP53, LRP1B, STK11, KEAP1, and CDKN2A. <br /><br />The study also analyzed the PD-L1 status in 732 cases, with 67.2% of cases being positive for PD-L1 and the remaining 32.8% being negative. This has implications for first-line immune checkpoint inhibitor monotherapy, as PD-L1 negative cases are ineligible.<br /><br />The findings of this study have therapeutic implications, especially for patients with co-alterations in genes such as STK11 and KEAP1, which are associated with worse outcomes. The study suggests that further drug development for KRAS inhibitors with central nervous system activity is needed.<br /><br />In summary, this study highlights the prevalence of KRAS subtype alterations in NSCLC patients with brain metastases. It provides insights into the most frequent KRAS alterations and co-mutations, and emphasizes the need for targeted therapies for patients with specific gene co-alterations.

Asset Subtitle

Faran Polani

Meta Tag

Speaker Faran Polani

Topic Pathology & Biomarkers: Genetic Biomarkers

Keywords

KRAS subtype alterations

non-small cell lung cancer

brain metastases

KRAS p.G12C

co-alterations

genes

TP53

LRP1B

STK11

KEAP1