The relevance of the reference range for EGFR testing in non-small cell lung cancer patients

Abstract

Introduction

Identifying mutations in the epidermal growth factor receptor (EGFR) gene is crucial for individualized treatment of non-small cell lung cancer (NSCLC) patients. Accordingly, several methodologies and instruments are now commercially available to detect these alterations. The aim of this study was to examine the performance of next generation sequencing (NGS) in detecting both common and uncommon EGFR gene mutations in advanced NSCLC patients.

Methods

We retrospectively retrieved molecular data from n = 1312 advanced stage NSCLC patients tested by our NGS DNA-based panel (namely SiRe® panel) from January 2018 to December 2022. We subsequently compared the NGS results with the reference ranges of the most popular real time PCR (RT-qPCR) assays (cobas® EGFR Mutation Test v2, EasyPGX® ready EGFR, Idylla™ EGFR mutation test, and therascreen® EGFR Plus RGQ).

Results

Overall, NGS detected n = 234 mutations in n = 192 (15.9 %) patients. Conversely, when these results were compared with the reference ranges of the four most common commercially available RT-qPCR assays, far fewer mutations were identified: n = 18 (9.4 %), n = 17 (8.9 %), n = 17 (8.9 %), and n = 18 (9.4 %) mutations. These results suggest that if patients were tested solely using RT-qPCR assays, a substantial proportion would have been ineligible for targeted therapies.

Conclusions

Our study highlights that NGS is able to identify a much higher number of actionable EGFR mutations than RT-qPCR approaches, thereby providing many more patients the opportunity to receive targeted EGFR treatments.