2022 World Conference on Lung Cancer (ePosters)-EP08.02-125. Tumor Suppressor Gene Alterations Identified at Disease Progression Impact Outcomes in Patients with EGFR-mutant Lung Cancer

EP08.02-125. Tumor Suppressor Gene Alterations Identified at Disease Progression Impact Outcomes in Patients with EGFR-mutant Lung Cancer

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A study conducted at Yale University School of Medicine focused on the impact of tumor suppressor gene (TSG) alterations on the outcomes of patients with EGFR-mutant lung cancer. The researchers aimed to understand the mechanisms of resistance acquisition and optimize EGFR-targeted therapy. The study included patients with EGFR-mutant non-small cell lung cancer (NSCLC) who had undergone comprehensive next-generation sequencing. The analysis revealed that mutations in TSGs, specifically beyond TP53, played a role in driving poor prognosis in patients with EGFR-mutant lung cancer. The most frequently altered additional TSGs in these cases were NF1, RB1, BRCA1, and PTEN. Notably, patients with TP53mut/TSGmut tumors had worse progression-free survival (PFS) and overall survival (OS) on both first-line and second-line EGFR tyrosine kinase inhibitors (TKIs) compared to TP53mut/TSGwt or TP53wt cases. Multivariate analysis confirmed that TP53mut/TSGmut status was independently associated with worse PFS and OS. These findings were further validated in a separate cohort of patients with EGFR-mutant NSCLC. The study suggests that identifying TSG alterations beyond TP53 can contribute significantly to risk stratification in EGFR-mutant lung cancer. Overall, the study provides important insights into the molecular and clinical heterogeneity of EGFR-mutant NSCLC and highlights the need for further characterization of TSG alterations to optimize treatment strategies.

Asset Subtitle

Paul Stockhammer

Meta Tag

Speaker Paul Stockhammer

Topic Metastatic Non-small Cell Lung Cancer - Molecular Targeted Treatments

Keywords

tumor suppressor gene alterations

EGFR-mutant lung cancer

resistance acquisition

EGFR-targeted therapy

next-generation sequencing

TP53

NF1

RB1

BRCA1

PTEN