| Summary: | Background: Assessment of actionable <i>EGFR</i> mutations is mandatory for treatment-naïve advanced or metastatic non-squamous lung carcinoma (NSLC), but the results need to be obtained in less than 10 working days. For rapid <i>EGFR</i> testing, an <i>EGFR</i>-specific polymerase chain reaction (PCR) assay is an alternative and simple approach compared to next generation sequencing (NGS). Here, we describe how a rapid <i>EGFR</i>-specific PCR assay can be implemented in a single laboratory center (LPCE, Nice, France) as reflex testing in treatment-naïve NSLC. Methods: A total of 901 biopsies from NSLC with more than 10% of tumor cells were prospectively and consecutively evaluated for <i>EGFR</i> mutation status between November 2017 and December 2019 using the Idylla system (Biocartis NV, Mechelen, Belgium). NGS was performed for nonsmokers with NSLC wild type for <i>EGFR</i>, <i>ALK</i>, <i>ROS1</i>, and <i>BRAF</i> and with less than 50% PD-L1 positive cells using the Hotspot panel (Thermo Fisher Scientific, Waltham, MA, USA). Results: Results were obtained from 889/901 (97%) biopsies with detection of <i>EGFR</i> mutations in 114/889 (13%) cases using the Idylla system. Among the 562 <i>EGFR</i> wild type tumors identified with Idylla, NGS detected one actionable and one nonactionable <i>EGFR</i> mutation. Conclusions: Rapid and targeted assessment of <i>EGFR</i> mutations in treatment-naïve NSLC can be implemented in routine clinical practice. However, it is mandatory to integrate this approach into a molecular algorithm that allows evaluation of potentially actionable genomic alterations other than <i>EGFR</i> mutations.
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