2022 World Conference on Lung Cancer (ePosters)-EP08.02-147. Clinical Outcomes in Patients with or without Cell Cycle Gene Alterations in EGFR mutated Non-Small Cell Lung Cancer

EP08.02-147. Clinical Outcomes in Patients with or without Cell Cycle Gene Alterations in EGFR mutated Non-Small Cell Lung Cancer

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This study aimed to investigate the clinical outcomes in patients with or without cell cycle gene alterations in EGFR mutated non-small cell lung cancer (NSCLC). The researchers conducted a retrospective study of 62 patients with EGFR exon 19 deletions, L858R and T790M mutations who were treated with tyrosine kinase inhibitors (TKIs) at a single tertiary medical center between 2010 and 2021. Tumor genomics were analyzed using the UCSF 500 Next Generation Sequencing Assay to identify cell cycle gene alterations. The clinical outcomes of patients with pre-TKI treatment cell cycle gene alterations (CC) were compared to those without (CC-).<br /><br />The main finding of the study was that concurrent cell cycle gene alterations were associated with worse disease control and progression-free survival in EGFR-mutated NSCLCs treated with an EGFR TKI. Patients in the CC- cohort had a longer median progression-free survival compared to those in the CC cohort (21.5 months vs. 13.8 months). The objective response rate to EGFR-TKI treatment was similar between the two cohorts, but the disease control rate was higher in the CC- cohort (100% vs. 81.8%). Biopsies performed at the time of disease progression revealed various genomic alterations, including p53 mutation, MET amplification, ALK fusion, RET fusion, NTRK fusion, RB1 mutation, CDKN2A/2B deep deletion, CDK 4 amplification, CCNE1 amplification, CDK4/6 amplification, RB1 alteration, and E2F3 amplification.<br /><br />These findings suggest that cell cycle gene alterations may enable tumor cells to develop resistance to TKI therapy and that targeting both EGFR and cell cycle alterations with combination therapies may lead to improved clinical outcomes. The study adds to the growing understanding of the mechanisms underlying resistance to TKIs in EGFR-mutated NSCLC and provides valuable insights for the development of more effective treatment strategies.

Asset Subtitle

Turja Chakrabarti

Meta Tag

Speaker Turja Chakrabarti

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

Keywords

clinical outcomes

cell cycle gene alterations

EGFR mutated non-small cell lung cancer

retrospective study

tyrosine kinase inhibitors

UCSF 500 Next Generation Sequencing Assay

disease control

progression-free survival

EGFR TKI

genomic alterations