2024 World Conference on Lung Cancer (WCLC) - Posters-P1.06B.06 Analysis of Antibody-Drug Conjugate Target Expression Across Genomic Subsets of Non-Small Cell Lung Cancer

P1.06B.06 Analysis of Antibody-Drug Conjugate Target Expression Across Genomic Subsets of Non-Small Cell Lung Cancer

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This study investigates the expression of antibody-drug conjugate (ADC) targets across different genomic subsets of non-small cell lung cancer (NSCLC) to better understand their potential efficacy. ADCs have emerged as an important treatment option in NSCLC, but their effectiveness is inconsistent, possibly due to variable target expression in tumors. The research aims to map the expression levels of ADC target proteins before and after targeted therapy, specifically in the context of genomic variations like EGFR mutations and ALK, ROS1, or RET fusions.<br /><br />The study utilized immunohistochemistry (IHC) to assess the expression of key ADC targets—MET, HER2, HER3, TROP2, and CEACAM5—in 106 tumor samples from 78 NSCLC patients. The results reveal that MET, CEACAM5, and TROP2 are more frequently expressed compared to HER2 and HER3, with the differences being statistically significant (p<0.001). Furthermore, the study found no substantial changes in ADC target expression levels pre- and post-tyrosine kinase inhibitor (TKI) therapy within a small cohort of EGFR- and fusion-driven NSCLC.<br /><br />The research involved a retrospective analysis of formalin-fixed, paraffin-embedded archival tumor samples, categorized by genotype including mutations in EGFR, ALK, ROS1, RET, and KRAS.<br /><br />The study underscores the need for further systematic assessment of ADC target expression across different genomic landscapes of NSCLC. Understanding these variations can inform the clinical development and potential success of ADC-based therapies. Future investigations may not only enhance therapeutic effectiveness but also tailor treatments to the genetic profile of individual tumors. The research was supported by grants from the National Cancer Institute, the Dana-Farber/Harvard Cancer Center, and other distinguished collaborations.

Asset Subtitle

Jessica Lin

Meta Tag

Speaker Jessica Lin

Topic Pathology & Biomarkers

Keywords

antibody-drug conjugate

NSCLC

genomic subsets

target expression

immunohistochemistry

EGFR mutations

ALK fusions

ROS1 fusions

RET fusions

tyrosine kinase inhibitor