2023 World Conference on Lung Cancer (Posters)-P2.09. Identification of Co-existing Genetic Alterations in Advanced Stage EGFR mutated NSCLC at Baseline and Disease Progression

P2.09. Identification of Co-existing Genetic Alterations in Advanced Stage EGFR mutated NSCLC at Baseline and Disease Progression - PDF(Abstract)

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This presentation discussed a study on the molecular mechanisms of treatment resistance among patients with advanced stage non-small cell lung cancer (NSCLC) undergoing epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy. The study aimed to investigate co-existing genetic alterations in addition to EGFR mutations that may contribute to treatment resistance. A total of 61 patients were included in the study, and their baseline tumor tissue biopsies and tissue or plasma samples obtained during tumor progression were analyzed using a targeted next-generation sequencing (NGS) panel. The results showed that EGFR T790M mutations were detected in 34.5% of patients at progression, while only founder mutations were detected in 54% of patients. Histological small cell transformation (SCT) was identified in 11.5% of patients, and it was found to occur significantly earlier than the acquisition of EGFR T790M mutations. The NGS analysis identified TP53 and RB1 mutations as the only genetic alterations present both at baseline and disease progression, while other alterations, such as PIK3CA, CDKN2A, and ATM, were detected only in post-TKI biopsies. The mutations in RB1 and TP53 correlated with the occurrence of small cell transformation. The study concluded that EGFR T790M mutations represented only a third of the causes of EGFR TKI resistance in the cohort, with a higher prevalence of histological small cell transformation compared to Western cohorts. The findings suggest the presence of co-existing mutations that may contribute to primary and secondary resistance mechanisms in response to EGFR TKI therapy.

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AMBER RATHOR

Meta Tag

Speaker AMBER RATHOR

Topic Metastatic NSCLC: Targeted Therapy - EGFR/HER2

Keywords

treatment resistance

non-small cell lung cancer

EGFR tyrosine kinase inhibitor

genetic alterations

EGFR mutations

next-generation sequencing

histological small cell transformation

TP53 mutations

RB1 mutations

EGFR TKI resistance