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(Slides)

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This study aimed to investigate the molecular mechanisms of treatment resistance in advanced stage non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. The study included EGFR mutant patients receiving EGFR tyrosine kinase inhibitor (TKI) therapy who developed disease progression. Sixty-two patients met the inclusion criteria and were analyzed using a targeted next-generation sequencing lung cancer panel. The results showed that EGFR T790M resistance mutation was detected in 35.4% of cases, founder mutations were detected in 53.2% of cases, and small cell histological transformation was observed in 11.4% of cases.<br /><br />The study found that EGFR acquired resistance T790M mutations represented only one third of the causes of EGFR TKI resistance mechanisms. There was a higher prevalence of histological small cell transformation. The study also identified additional alterations such as PIK3CA and CDKN2A in post-TKI biopsy samples. These alterations, along with TP53 and NF1, were present at both baseline and subsequent biopsy on disease progression.<br /><br />The median time to progression-free survival (PFS) for the patient cohort was 12.5 months. Cases with small cell transformation had significantly shorter median PFS of 6 months compared to other resistance mechanisms.<br /><br />Overall, this preliminary study suggests that co-existing mutations with baseline EGFR may be linked to primary and secondary resistance mechanisms in response to EGFR TKI therapy. The findings highlight the importance of understanding the molecular mechanisms of treatment resistance in EGFR mutated NSCLC to develop more effective therapeutic strategies.

Asset Subtitle

AMBER RATHOR

Meta Tag

Speaker AMBER RATHOR

Topic Metastatic NSCLC: Targeted Therapy - EGFR/HER2

Keywords

molecular mechanisms

treatment resistance

NSCLC

EGFR mutations

tyrosine kinase inhibitor

T790M resistance mutation

small cell histological transformation

next-generation sequencing

progression-free survival

therapeutic strategies