Liquid Biopsy Monitoring Of EGFR T790M in Advanced Non-Small Cell Lung Cancer

Acquired resistance to first- and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in advanced EGFR-mutated non-small cell lung cancer (NSCLC) is most commonly mediated by the secondary EGFR T790M mutation. Identification of this resistance mechanism is clinically relevant, as it may guide subsequent treatment strategies. However, repeat tissue biopsy at disease progression is often limited by tumor inaccessibility, patient condition, or procedural risk. Plasma-based analysis of circulating tumor DNA (ctDNA) offers a minimally invasive alternative for molecular reassessment. This retrospective real-world study evaluates the implementation of plasma EGFR testing for the detection of acquired T790M mutation in routine clinical practice in Tunisia. The study focuses on the detection rate of T790M at progression, the added value of repeated liquid biopsy sampling in initially negative cases, and the relationship between T790M emergence and baseline clinical or molecular characteristics. In addition, longitudinal patterns of T790M appearance, persistence, or loss across serial plasma samples are explored to better understand resistance dynamics under TKI selective pressure. The association between T790M status and progression-free survival is also assessed. By integrating molecular results with longitudinal clinical follow-up, this study seeks to characterize real-world patterns of acquired resistance and to evaluate the practical contribution of plasma-based EGFR testing to therapeutic decision-making.