Abstract 5898: Investigation of EGFR mutations in lung cancer patients through liquid biopsy analysis

Objective: Lung cancer is the leading cause of cancer-related mortality in Taiwan as of 2023. Early diagnosis and continuous monitoring are critical for improving patient prognosis. Studies indicate that approximately 50% of lung cancer patients in Asia have EGFR gene mutations. Among patients receiving first- and second-generation targeted therapies, over 50% develop resistance due to T790M gene mutations. The gold standard for lung cancer diagnosis involves pathological tissue examination, including cytological analysis, immunohistochemistry, and genetic testing. Recently, blood-based liquid biopsy for EGFR qPCR gene mutation analysis has emerged as a novel method due to its rapid turnaround time and reduced invasiveness. This study aims to compare EGFR gene qPCR mutation detection via liquid biopsy with tissue biopsy results and assess the clinical utility of liquid biopsy for EGFR qPCR testing. Methods: From March 2018 to April 2020, we collected 416 peripheral blood samples via venipuncture for EGFR liquid biopsy using the Cobas EGFR Mutation Test v2. Simultaneously, corresponding tissue biopsy samples were obtained for EGFR genetic analysis using Sanger or MASS sequencing. We compared results from both testing methods and statistically evaluated sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and concordance rate. Results: Among the 416 samples, 280 were from females and 136 from males, aged 32 to 92 years (average age 65). The EGFR mutation test results included: negative (221 cases), deletion in exon 19 (Del 19) (65 cases), L858R (65 cases), Del 19+T790M (34 cases), Del 19+L858R (21 cases), T790M (2 cases), and other mutations (8 cases). Of the 416 cases, 230 lacked available pathological tissue reports for comparison. In the 186 cases with pathology reports, we noted various timing discrepancies between liquid and tissue biopsies. Among 94 patients with both liquid biopsy and tissue biopsy results, the overall concordance rate was 77.7%. Using tissue biopsy as the gold standard, sensitivity, specificity, PPV, NPV, and concordance rates for detecting Del 19, L858R, and T790M mutations were as follows: Del 19 (0.83/1/1/0.86/0.92), L858R (0.67/1/1/0.87/0.89), T790M (0.38/0.93/0.64/0.81/0.79). Conclusion: EGFR liquid biopsy qPCR can be effectively utilized at lung cancer diagnosis and for monitoring drug resistance during targeted therapy. Compared to tissue biopsy, liquid biopsy qPCR using peripheral blood is a less invasive procedure with improved efficacy and an overall concordance rate deemed clinically acceptable. Citation Format: Pin-fei Wei, Shang-Gin Wu. Investigation of EGFR mutations in lung cancer patients through liquid biopsy analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5898.