Coverage of actionable alterations in non-small cell lung cancer by hybrid capture-based FoundationOne®CDx compared with amplicon-based OncomineDX.

INTRODUCTION: FoundationOne®CDx (F1CDx) and Oncomine Dx target test (ODxTT) are commercially available oncology biomarker assays that apply different next-generation sequencing methodologies used to identify predictive markers for therapy selection in non-small cell lung cancer (NSCLC). We hypothesized that F1CDx can detect a higher number of actionable alterations compared with the ODxTT assay. MATERIALS AND METHODS: We compared the prevalence of genomic alterations (GA) in a real-world NSCLC cohort tested by F1CDx to the theoretical detection by ODxTT, based on publicly available coverage specifications. The clinical actionability of GA was assessed based on NCCN treatment guidelines and FDA oncology drug approvals. RESULTS: KRAS G12C, EGFR mutations, and MET mutations were among the most frequent actionable alterations detected in a large genomic dataset of NSCLC data assayed by the F1CDx test. The ODxTT specifications indicate that ODxTT detects all BRAF and KRAS FDA-approved alterations detected by F1CDx and subsets of the following clinically significant markers: EGFR 83%, RET 76%, ROS1 74%, and ERBB2 38%. In addition, ODxTT had no coverage for actionable genomic findings in ALK, MET, NTRK1/2/3, TMB, or MSI-High status. In this study, the ODxTT assay may fail to report at least one of the clinically actionable biomarkers in 42% of tissue samples compared to F1CDx. DISCUSSION: In summary, in advanced NSCLC, hybrid capture-based NGS, such as F1CDx, may capture more actionable genomic alterations as compared with ODxTT, an amplicon-based NGS.