2024 Hot Topic in Basic & Translational Science: Tolerance & Resistance to Targeted Therapy in NSCLC - Posters-PP01.07: Alterations in Tumor Suppressor Genes are Associated With Aggressive Disease Phenotypes in EGFR-Mutant NSCLC

PP01.07: Alterations in Tumor Suppressor Genes are Associated With Aggressive Disease Phenotypes in EGFR-Mutant NSCLC

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This study focuses on the impact of tumor suppressor gene (TSG) alterations in patients with non-small cell lung cancer (NSCLC) carrying EGFR mutations. The research encompassed a large cohort of 3,543 patients with classical EGFR mutations, namely L858R and exon 19 deletion (ex19del). It was found that co-occurring TSG alterations such as TP53, RBM10, and RB1 were frequent, with TP53 being present in 60.2% of cases.<br /><br />Key findings include:<br />1. Allele-specificity was not observed with most TSGs between the L858R and ex19del mutations.<br />2. TSG alterations did not increase post-TKI therapy, indicating they are unlikely contributors to acquired resistance against tyrosine kinase inhibitors (TKIs).<br />3. Certain TSG mutations were linked to poorer outcomes with specific therapies: TP53 and NF1 correlated with reduced overall survival (OS) when patients were treated with osimertinib, while TP53, RB1, and PTEN mutations were detrimental in chemotherapy-treated patients.<br />4. Notably, RBM10 mutations were more frequent in L858R versus ex19del EGFR mutations.<br /><br />The study suggests that patients with specific TSG alterations might benefit more from combination regimens rather than single-agent treatments like osimertinib or platinum-based chemotherapy. The findings underscore the importance of identifying specific co-mutations that could guide more tailored and effective treatment strategies in EGFR-mutant NSCLC cases.<br /><br />Additionally, TP53 mutations were more prevalent in metastatic rather than primary NSCLC tumors, indicating a possible role in disease progression. These insights prompt further investigation into optimal treatment combinations for patients with aggressive disease phenotypes marked by these genetic alterations.

Asset Subtitle

Paul Stockhammer

Keywords

tumor suppressor gene

non-small cell lung cancer

EGFR mutations

TP53

RBM10

RB1

osimertinib

chemotherapy

TKI resistance

metastatic NSCLC