Multicenter Evaluation of the Fully Automated PCR-Based Idylla EGFR Mutation Assay on Formalin-Fixed, Paraffin-Embedded Tissue of Human Lung Cancer

Abstract

Before initiating treatment of advanced nonesmall-cell lung cancer with tyrosine kinase inhibitors (eg, erlotinib, gefitinib, osimertinib, and afatinib), which inhibit the catalytic activity of epidermal growth factor receptor (EGFR), clinical guidelines require determining the EGFR mutational status for activating (EGFR exons 18,19,20,or 21) and resistance (EGFR exon 20) mutations. The EGFR resistance mutation T790M should be monitored at cancer progression. The Idylla EGFR Mutation Assay, performed on the Idylla molecular diagnostics platform, is a fully automated (<2.5 hours turnaround time) sample-to-result molecular test to qualitatively detect 51 EGFR oncogene point mutations, deletions, or insertions. In a 15-center evaluation, Idylla results on 449 archived formalin-fixed, paraffin-embedded tissue sections, originating from nonesmall-cell lung cancer biopsies and resection specimens, were compared with data obtained earlier with routine reference methods, including next-generation sequencing, Sanger sequencing, pyrosequencing, mass spectrometry, and PCR-based assays. When results were discordant, a third method of analysis was performed, when possible, to confirm test results. After confirmation testing and excluding invalids/errors and discordant results by design, a concordance of 97.6% was obtained between Idylla and routine test results. Even with <10 mm 2 of tissue area, a valid Idylla result was obtained in 98.9% of the cases. The Idylla EGFR Mutation Assay enables sensitive detection of most relevant EGFR mutations in concordance with current guidelines, with minimal molecular expertise or infrastructure.

Testing EGFR with Idylla on Cytological Specimens of Lung Cancer: A Review

“…In a subsequent clinical implementation phase, they report a sensitivity of 95.6% (84.9–99.5%) and a specificity of 100%. The other studies either did not assess sensitivity and specificity or did so but with an older reference method [ 65 , 67 ]. These results are comparable to those obtained with histological samples [ 68 ].…”

Ultrarapid EGFR Mutation Screening Followed by Comprehensive Next-Generation Sequencing: A Feasible, Informative Approach for Lung Carcinoma Cytology Specimens With a High Success Rate

“…The platform can be easily integrated into any clinical molecular diagnostic laboratory, enabling rapid triaging for critical molecular markers. Although several publications have already documented the use of Idylla for FFPE biopsy samples, [39][40][41][42][43][44][45] descriptions of the suitability of cytology samples for this platform have remained confined to a few small, proof-of-principle studies, 46 and the corresponding performance characteristics, clinical validation, and extended clinical experience have remained largely undefined. The application to cytologic material is ideal, however, as it can easily address the issues of TAT and also provide rapid assessment in samples that are very scant and otherwise unsuitable for any other kind of testing.…”

Predictive molecular pathology in the time of coronavirus disease (COVID-19) in Europe

“…As far as analytical methodological procedures are concerned, it is remarkable that in the 33.3% of the laboratories favoured less cumbersome RT-PCR-based methodologies, including fully automated platforms that require limited hands-on-times. 16 The reason behind this switch in testing strategies may reflect the need to reduce the number of staff personnel during the emergency and the fact that more simple genotyping workflows better adapt the need to maintain social distancing measures. These latter are more difficult to be strictly respected when NGS is adopted as more than one operator may be involved in different analytical phases.…”