The efficacy of T790M mutation testing in liquid biopsy-Real clinic data
Paweł Krawczyk1, Luiza Grzycka-Kowalczyk2, Justyna Błach1,3
1Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Lublin, Poland.
Abstract:
Osimertnib is still widely used in the treatment of NSCLC patients who have previously received erlotinib, gefitinib or afatinib and have developed resistance to these drugs mediated by the T790M mutation in exon 20 of EGFR gene. We assessed the results of T790M mutation testing in liquid biopsy by Entrogen test and real-time PCR technique in routine clinical practice. Analysis was conducted in 73 plasma samples from 41 patients with locally advanced or metastatic lung adenocarcinoma treated with first- or second-generation of EGFR TKIs. We detected T790M mutation in 18 patients (43.9% of patients, 24.6% positive tests in 73 samples). The incidence of T790M mutation in liquid biopsy was significantly higher in patients with T3-T4 tumors compared to patients with T0-T2 tumors (p = 0.0368, χ2 = 4.36). Median PFS at the time of progression according to RECIST was significantly (p = 0.0444) higher in patients with T790M mutation than in patients without this mutation (22.5 vs. 15 months). Our results confirmed that T790M mutation is more often detected in patients with a large tumor spreading in the chest and with the long duration of response to first- or second generation of EGFR TKIs. The low sensitivity of the real-time PCR technique in T790M mutation detection could be partially compensated by repeating the tests.
Insights
Testing for the T790M mutation in EGFR gene using liquid biopsy is crucial for non-small cell lung cancer (NSCLC) patients. Detecting this mutation indicates a better response to targeted therapies.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Osimertinib is a key treatment for non-small cell lung cancer (NSCLC) with EGFR T790M mutations.
- Resistance to first- and second-generation EGFR TKIs often involves the T790M mutation.
- Liquid biopsy offers a minimally invasive method for detecting actionable mutations.
Purpose of the Study:
- To evaluate the clinical utility of T790M mutation testing in liquid biopsy for NSCLC patients.
- To compare the performance of Entrogen test and real-time PCR for T790M detection.
- To correlate T790M mutation status with tumor characteristics and treatment outcomes.
Main Methods:
- Analysis of 73 plasma samples from 41 NSCLC patients treated with first- or second-generation EGFR TKIs.
- T790M mutation testing performed using Entrogen test and real-time PCR.
- Correlation of mutation detection with tumor stage (TNM) and progression-free survival (PFS) based on RECIST criteria.
Main Results:
- T790M mutation detected in 43.9% of patients (18/41) and 24.6% of samples (18/73).
- Higher incidence of T790M mutation in patients with advanced T3-T4 tumors (p=0.0368).
- Median PFS was significantly higher in T790M-positive patients (22.5 months) compared to T790M-negative patients (15 months) (p=0.0444).
Conclusions:
- T790M mutation detection in liquid biopsy is valuable for guiding NSCLC treatment decisions.
- The presence of T790M mutation correlates with larger tumor size and longer response duration to prior EGFR TKIs.
- Real-time PCR sensitivity for T790M detection may be improved by test repetition.
