2023 World Conference on Lung Cancer (Posters)-EP11.03. Impact of KRAS Mutation Subtype and Comutations across PD-L1 Levels in aNSCLC Patients Treated with (Chemo)Immunotherapy

EP11.03. Impact of KRAS Mutation Subtype and Comutations across PD-L1 Levels in aNSCLC Patients Treated with (Chemo)Immunotherapy - PDF(Slides)

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This study examined the impact of KRAS mutations and comutations with STK11 and KEAP1 across different PD-L1 expression levels in patients with non-small cell lung cancer (NSCLC) treated with (chemo)immunotherapy. The researchers used a nationwide observational database to assess the frequency of KRAS mutations and comutations across different PD-L1 levels, and to evaluate the association between these mutations and overall survival (OS) and progression-free survival (PFS).<br /><br />They found that KRAS mutations were associated with worse OS only in patients with PD-L1 negative tumors. This association was driven by comutations with STK11 and KEAP1, which were more common in patients with PD-L1 negative tumors. KRAS mutations were enriched in the PD-L1 50% cohort, while comutations with STK11 and KEAP1 were enriched in the PD-L1 0% cohort. KRAS mutations were associated with worse OS and PFS only in the PD-L1 negative group.<br /><br />Furthermore, KRAS comutations with KEAP1 and STK11 were more strongly associated with worse OS in the PD-L1 negative and PD-L1 low subgroups compared to the PD-L1 high subgroup. Triple mutations in KRAS/KEAP/STK11 were associated with the worst outcomes. These findings suggest the need for better evaluation of resistance mechanisms and improvement in therapeutic strategies for patients with PD-L1 negative NSCLC, especially those with triple mutations in KRAS/KEAP/STK11.<br /><br />The study also identified characteristics associated with KRAS mutations, such as being more likely to be female, having a smoking history, and having nonsquamous histology compared to KRAS wild-type.<br /><br />Overall, this study highlights the complex interplay between KRAS mutations, comutations with STK11 and KEAP1, and PD-L1 expression in predicting outcomes in patients with NSCLC treated with (chemo)immunotherapy.

Asset Subtitle

Jessica Bauman

Meta Tag

Speaker Jessica Bauman

Topic Metastatic NSCLC: Immunotherapy - Retrospective

Keywords

KRAS mutations

comutations

STK11

KEAP1

PD-L1 expression

non-small cell lung cancer

NSCLC

chemoimmunotherapy

overall survival

progression-free survival