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(Abstract)

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This study aimed to investigate the impact of different KRAS mutation subtypes and co-mutations on outcomes in patients with metastatic non-small cell lung cancer (NSCLC) treated with immunotherapy. The researchers analyzed data from a database of NSCLC patients who received frontline immunotherapy or chemoimmunotherapy. They compared overall survival (OS) and progression-free survival (PFS) between groups defined by KRAS mutation, subtype, and co-mutation status, stratified by programmed death-ligand 1 (PD-L1) levels. <br /><br />The study included 2,844 patients with a mean age of 69 years, and most were White and had a smoking history. PD-L1 status was evenly distributed among different levels. KRAS mutations were found in 37.8% of patients, with the most common subtypes being G12C, G12V, and G12D. Co-mutations with STK11, TP53, and KEAP1 were also observed in varying frequencies. <br /><br />Overall, KRAS mutations were not associated with OS or PFS. However, when stratified by PD-L1 levels, KRAS mutations were associated with worse PFS and OS in the PD-L1 negative subgroup, regardless of KRAS subtype. In the PD-L1 high subgroup, no significant difference in survival was observed between KRAS mutated and wild-type patients, except for G12V, which had worse OS compared to G12C. <br /><br />Additionally, in the PD-L1 negative subgroup, patients with double or triple co-mutations involving KRAS, STK11, KEAP1, and TP53 had worse survival compared to wild-type patients. These associations were not seen in PD-L1 positive subgroups. <br /><br />In conclusion, the impact of KRAS mutations in NSCLC varies depending on mutation subtype, PD-L1 status, and co-mutation status. G12C subtype was associated with better OS compared to G12V in the PD-L1 high subgroup, while co-mutations involving KRAS, STK11, KEAP1, and TP53 were associated with particularly poor outcomes in the PD-L1 negative subgroup. These findings suggest that different KRAS subtypes and co-mutations may define different treatment-resistant groups in NSCLC patients, highlighting the need for personalized therapeutic approaches.

Asset Subtitle

Jessica Bauman

Meta Tag

Speaker Jessica Bauman

Topic Metastatic NSCLC: Immunotherapy - Retrospective

Keywords

KRAS mutation

subtypes

co-mutations

metastatic non-small cell lung cancer

NSCLC

immunotherapy

overall survival

progression-free survival

PD-L1 levels

database analysis