2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.11A.06 Somatic Gene Changes Associated with Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer

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The study presented in Poster #3074 explores the influence of somatic gene changes on the response to immune checkpoint inhibitors (ICIs) in treating non-small cell lung cancer (NSCLC). ICIs have significantly advanced lung cancer treatment, though their effectiveness is limited to certain patients. This research seeks to identify predictive biomarkers that could refine patient selection and enhance therapeutic strategies by examining genetic alterations.<br /><br />During 2015-2023, NSCLC patients (n=550) who received at least three doses of ICIs were evaluated. Patients were classified as non-progressors (exhibiting complete or partial responses or stable disease) or progressors (demonstrating disease progression) through RECIST 1.1 coding and clinical review. Key genes studied include KRAS, NF1, STK11, TP53, and TSC1/2, which are potentially significant for predicting ICI responsiveness and understanding its biological basis.<br /><br />Findings indicated that 277 out of 550 patients exhibited somatic changes in 1-46 genes, with a median of three gene alterations. Non-Caucasians displayed a higher frequency of gene changes than Caucasians, and a larger proportion of altered genes was observed in tumors with low PDL1 expression compared to those with high PDL1 levels. The genes most frequently altered among tested patients were TP53, KRAS, CDKN2A, APC, and ATM.<br /><br />Moreover, the study noted a significant association between genetic changes in NF1, SMAD1, and TSC1 genes with a reduced likelihood of ICI response. Additionally, within the low PD-1 group and high PD-1 group, specific gene alterations were linked to a lack of response to ICI therapy.<br /><br />The study suggests further development of predictive models that incorporate these genetic alterations alongside other clinical factors to improve patient stratification for ICI therapy. Exploration of PDL1 expression and specific gene changes in context with ICI responsiveness is also recommended for future directions.

Asset Subtitle

Akhil Goud Pachimatla

Meta Tag

Speaker Akhil Goud Pachimatla

Topic Metastatic Non-small Cell Lung Cancer – Immunotherapy

Keywords

somatic gene changes

immune checkpoint inhibitors

non-small cell lung cancer

predictive biomarkers

genetic alterations

PDL1 expression

KRAS

TP53

NF1

ICI response