367P - Detection of epidermal growth factor receptor mutations (EGFR-mut) from cell-free DNA in pleural effusion (PE-DNA) of patients with non-small cell lung cancer (NSCLC)

Background

EGFR-mut status is pivotal to select NSCLC patient for EGFR tyrosine kinase inhibitors (EGFR-TKI). Obtaining adequate tissue for genomic analysis is challenging thus plasma cell-free DNA (Plasma-DNA)-based genotyping of EGFR-mut is a reasonable alternative. Sensitivity varies between 60 to 80%; specificity is consistently above 90%. Emerging evidence shows that pleural effusion (PE) is an alternative rich source of cfDNA for EGFR-mut testing despite negative cytology in PE samples. Droplet digital PCR (ddPCR) is a sensitive technique and the objective of our study is to examine the diagnostic utility of EGFR genotyping in PE using ddPCR.

Methods

Patients with histologically proven advanced stage NSCLC and PE are eligible. 10 ml of blood and 10 ml of PE were collected after consent. We used ddPCR to detect the EGFR mutations exon 19 del (e19del), exon 21 L858R mut (e21-L858R), exon 20 T790M (e20-T790M) in plasma and PE samples. We used Cobas® EGFR Mutation Test v2 or the “Scorpion-ARMS” therascreen® EGFR RotorGene Q (RGQ) PCR Kit to detect EGFR-mut in tumour samples.

Results

We enrolled 127 patients between November 2016 and June 2020. M vs F = 67 vs 60. Tumor tissue positive for EGFR-mut in 31 (40%) of 77 EGFR-TKI-naïve patients (e19del in 7; e21-L858R in 24; e20-T790M in 1) In the 50 EGFR-TKI resistant NSCLC, tumor sample for EGFR-mut analysis were not available in 13, wild-type in 5, e19del in 20, e21-L858R-mut in 12 and e20 T790M in 14. Diagnostic utility is summarized in the table. Detection rate of T790M is 15% (19/126) in plasma and 27% (34/127) in PE. We found 11 patients with negative T790M plasma samples but tested positive in PE-DNA, and vice versa, 2 samples. Concordance rate of T790M testing between plasma-DNA and PE-DNA is 0.86. Table: 367P

Conclusions

Testing of cfDNA in PE for EGFR mutation including e20-T790M is feasible and highly sensitive, and the concordance to plasma and tumor mutation status is high.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

T.C. Kwong, P.Y. Lo: Full/Part-time employment: Sanomics Limited. All other authors have declared no conflicts of interest.