Simulation analysis of EGFR mutation detection: Oncomine Dx target test and AmoyDx panel impact on lung cancer treatment decisions

Abstract

Lung cancer is a leading cause of cancer-related deaths worldwide. Epidermal growth factor receptor (EGFR) driver mutations are crucial for treatment decisions for patients with non-small cell lung cancer (NSCLC). This study aimed to assess the differences in EGFR mutation detection between two companion diagnostic (CDx) tests-the Oncomine Dx Target Test (ODxTT) and the AmoyDx Pan Lung Cancer PCR Panel-and their impact on treatment applicability. To this end, we used an in-house targeted sequencing dataset of 282 samples from 127 EGFR-mutated NSCLC patients to simulate the concordance between the EGFR variants targeted by the ODxTT and AmoyDx panel, the oncogenicity of the variants, and their therapeutic potential. Of the 216 EGFR mutations identified by the in-house panel, 51% were detectable by both CDx tests, 3% were specific to ODxTT, and 46% were not targeted by either test. Most non-targeted mutations did not have oncogenicity and were located outside exons 18-21. Notably, 95% of the mutations detectable by both tests had potential oncogenicity. Furthermore, among the 96 patients harboring actionable EGFR mutations, 97% had mutations detectable by both CDx tests and 1% by ODxTT, while 2% had mutations not covered by either test. These findings suggest that while both CDx tests are effective in detecting almost all actionable EGFR mutations, ODxTT provides slightly broader coverage. These results emphasize the importance of selecting appropriate CDx tests to inform treatment decisions for EGFR-positive NSCLC patients.

Figure 1

EGFR mutations targeted by CDx tests. (A) Lollipop plot showing the location of amino acid changes in EGFR mutations identified in the in-house panel. Green circles represent missense mutations, black circles represent truncation mutations, and brown circles represent in-frame mutations. The height corresponds to the number of samples in which EGFR mutations were detected. (B) The heatmap shows a list of EGFR mutations in each sample. The vertical axis represents the samples, and the horizontal axis represents the amino acid changes. The top annotations indicate the exon, mutation type, oncogenicity, targeted mutations for ODxTT and AmoyDx panel, mutations registered as actionable in CIViC, and mutations registered as actionable in OncoKB. (C) The variable tree diagram categorizes the EGFR mutations (total of 216 mutations) into targeted mutations for testing (green layer) and oncogenicity (orange layer).

Figure 2

Relationship between actionable mutations covered by CDx tests and clinical cases. Variable tree diagram classifying lung cancer patients (total of 127 cases) with EGFR mutations into cases with actionable mutations according to CIViC and OncoKB (purple layer) and cases with targeted mutations for testing (green layer).