Real-World Performance of the EasyPGX® Ready Epidermal Growth Factor Receptor Assay for Genomic Testing of Non-Small Cell Lung Cancer Samples

<b>Background/Objectives</b>: Activating epidermal growth factor receptor (<i>EGFR</i>) variants is the most common targetable alteration in non-small cell lung cancer (NSCLC). Clinical decision-making requires fast and reliable detection of <i>EGFR</i> variants in early and advanced NSCLC, but limited available tissue necessitates tissue-sparing approaches and optimized sample management. The objective of this study was to assess the performance of the commercial EasyPGX^® ready EGFR assay using real-world clinical NSCLC samples. <b>Methods</b>: A consecutive cohort of 804 non-squamous NSCLC samples was prospectively analyzed with the real-time quantitative polymerase chain reaction (RT-qPCR)-based EasyPGX^® ready EGFR assay (Diatech Pharmacogenetics, Jesi, Ancona, Italy) and compared to next-generation sequencing (NGS) assays. <b>Results</b>: NGS revealed conclusive results in 99.7% samples, of which 11.1% had at least one <i>EGFR</i> variant. The most common variants were exon 19 deletions and p.L858R. The RT-qPCR-based assay identified <i>EGFR</i> variants with high accuracy (overall concordance rate 94.3%) over a broad range of clinical sample types, variant allele frequencies, tumor cell contents and deoxyribonucleic acid (DNA) input amounts. <b>Conclusions</b>: This study demonstrates that the EasyPGX^® ready EGFR assay is a valid approach for the rapid detection of common <i>EGFR</i> variants in real-world clinical NSCLC samples with DNA inputs as low as 5 ng (less than the 15 ng recommended by the manufacturer), improving sample management in small specimens with limited quantity of nucleic acids.