WCLC 2025 - Posters & ePosters-EP.06.49 Analysis of EGFR Mutations Using Highly Sensitive Digital Droplet PCR for EGFR Mutation-Positive NSCLC

Pdf Summary

This prospective single-institution study evaluated the impact of the EGFR T790M mutation, detected via highly sensitive digital droplet PCR (ddPCR) prior to treatment, on the efficacy of EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced or recurrent EGFR mutation-positive non-small cell lung cancer (NSCLC). The study enrolled 21 patients, predominantly adenocarcinoma, median age 72, including both smokers and non-smokers. Tumor tissue samples were analyzed before EGFR-TKI therapy using ddPCR to quantify the T790M mutation with a defined positivity cutoff.<br /><br />Results showed that 6 patients were ddPCR positive for T790M, 7 indeterminate, and 8 negative. No germline T790M carriers were identified. Patients with ddPCR-detected T790M tended to have better progression-free survival (PFS) and overall survival (OS) compared to non-positive cases, a trend observed regardless of treatment with osimertinib or other EGFR-TKIs. This suggests that ddPCR T790M positivity may indicate a tumor biology more dependent on EGFR T790M-mediated resistance mechanisms. However, limited re-biopsy data after resistance development prevented confirmation that initial ddPCR detection predicts emergent T790M at resistance.<br /><br />The study cohort had a relatively older age and higher smoking rate, corresponding to a poorer prognosis population with shorter PFS and OS overall. Despite this, the ddPCR assay allowed precise quantification of T790M mutation load prior to treatment initiation, offering a potential predictive biomarker for EGFR-TKI response. The findings support that ddPCR detection of pretreatment T790M mutation might help identify patients likely to benefit from targeted therapies, including osimertinib.<br /><br />In conclusion, ddPCR offers a highly sensitive method to detect low-abundance EGFR T790M mutations before therapy, and positivity correlates with clinical outcomes. Larger studies are needed to validate ddPCR T790M as a predictive biomarker guiding EGFR-TKI treatment decisions in NSCLC. The study was funded by Boehringer Ingelheim, which had no influence on study design or results interpretation.

Asset Subtitle

Shinnosuke Takemoto

Meta Tag

Speaker Shinnosuke Takemoto

Topic Pathology and Biomarkers

Keywords

EGFR T790M mutation

digital droplet PCR

ddPCR

EGFR-tyrosine kinase inhibitors

EGFR-TKIs

non-small cell lung cancer

NSCLC

progression-free survival

overall survival

osimertinib