2022 World Conference on Lung Cancer (ePosters)-EP08.02-174. RET Fusions as Primary Oncogenic Drivers and Secondary Acquired Resistance to EGFR TKI in a Large Cohort of Non-Small-Cell Lung Cancers

EP08.02-174. RET Fusions as Primary Oncogenic Drivers and Secondary Acquired Resistance to EGFR TKI in a Large Cohort of Non-Small-Cell Lung Cancers

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A study was conducted to analyze the incidence and characteristics of RET fusions in non-small-cell lung cancer (NSCLC) patients, both at baseline and after developing resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). The tumor specimens and plasma samples of RET fusion positive patients were analyzed using targeted next-generation sequencing. The study found that primary RET fusions were more commonly associated with females and younger age. KIF5B-RET was the most common fusion in baseline RET patients, while CCDC6-RET was the most common fusion in patients who acquired RET fusions after resistance to EGFR-TKIs. The study also identified co-occurring genetic alterations and pathway-level associations with RET fusions. The incidence of RET fusions was significantly higher in EGFR-mutated NSCLC patients treated with 3rd-generation EGFR-TKIs compared to those treated with 1st- and/or 2nd-generation EGFR-TKIs. The study also found that patients with bypass pathway alterations or RB1/TP53 co-mutations had significantly shorter progression-free survival. RET fusions occur in 1-2% of NSCLC patients, and their role as primary oncogenic drivers and secondary resistance mechanisms to EGFR-TKIs has been established. The study provides insights into the genetic architecture of primary and secondary RET fusions in NSCLC and may guide treatment selection for EGFR-mutated NSCLC patients. The work was supported by the Science and Technology Project of Nantong City.

Asset Subtitle

Chunyue Wang

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Speaker Chunyue Wang

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

Keywords

RET fusions

non-small-cell lung cancer

NSCLC

EGFR tyrosine kinase inhibitors

EGFR-TKIs

targeted next-generation sequencing

KIF5B-RET

CCDC6-RET

genetic alterations

pathway-level associations