Longitudinal Liquid Biopsy Monitoring of EGFR T790M Resistance in Advanced Non-Small Cell Lung Cancer: Real-World Data From Tunisia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Detection rate of EGFR T790M mutation in plasma at disease progression
研究概览
简要总结
The goal of this retrospective observational study is to assess the clinical utility of plasma-based EGFR testing for detection and longitudinal monitoring of the acquired T790M resistance mutation in patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC) treated with first- or second-generation EGFR tyrosine kinase inhibitors in routine clinical practice in Tunisia.
The main questions it aims to answer are:
- What is the detection rate of EGFR T790M mutation in plasma at the time of disease progression?
- Does repeated liquid biopsy increase the cumulative detection of T790M?
- Is T790M emergence associated with baseline clinical and molecular characteristics?
- Is T790M status associated with progression-free survival? Participants underwent plasma sampling for circulating tumor DNA analysis during follow-up, and clinical and molecular data were retrospectively collected from medical records to evaluate mutation dynamics and outcomes.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Retrospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed advanced (stage IIIB/IV) non-small cell lung cancer
- •Documented activating EGFR mutations
- •Disease progression on first- or second-generation EGFR TKIs
排除标准
- •Prior treatment with third-generation EGFR TKIs before plasma sampling
- •Lack of follow-up clinical data
结局指标
主要结局
Detection rate of EGFR T790M mutation in plasma at disease progression
时间窗: From initiation of first- or second-generation EGFR-TKI therapy until the first documented radiological disease progression at which plasma EGFR T790M testing is performed, assessed up to 36 months.
Proportion of patients with detectable T790M in plasma at the time of radiological progression.
Cumulative detection of T790M with repeated liquid biopsy
时间窗: From the initial negative plasma EGFR T790M result at radiological disease progression until detection of T790M on repeat liquid biopsy testing during follow-up, assessed up to 36 months.
Incremental T790M detection in patients with initially negative plasma results who underwent additional testing.
次要结局
- Association of T790M emergence with baseline characteristics(Baseline defined at the time of initiation of first- or second-generation EGFR-TKI therapy, before treatment exposure)
- Progression-free survival by T790M status(From initiation of first- or second-generation EGFR-TKI therapy until the first radiologically confirmed disease progression, assessed up to 36 months.)
研究者
Soumaya RAMMEH
Professor
Faculty of Medicine of Tunis