Search

Background Genomic fusions are potent oncogenic drivers across cancer types and many are targetable. We demonstrate the clinical performance of DNA-based comprehensive genomic profiling (CGP) for detecting targetable fusions. Materials and Methods We analyzed targetable fusion genes in >450 000 tissue specimens profiled using DNA CGP (FoundationOne CDx, FoundationOne). Using a de-identified nationwide (US-based) non–small cell lung cancer (NSCLC) clinico-genomic database, we assessed outcomes in patients with nonsquamous NSCLC (NonSqNSCLC) who received matched therapy based on a fusion identified using DNA CGP. Lastly, we modeled the added value of RNA CGP for fusion detection in NonSqNSCLC. Results We observed a broad diversity of fusion partners detected with DNA CGP in conjunction with targetable fusion genes (ALK , BRAF , FGFR2 , FGFR3 , NTRK1/2/3 , RET , and ROS1). In NonSqNSCLC with oncogenic ALK , NTRK , RET , and ROS1 fusions detected by DNA CGP, patients treated with a matched tyrosine kinase inhibitor had better real-world progression-free survival than those receiving alternative treatment regimens and benefit was observed regardless of the results of orthogonal fusion testing. An estimated 1.3% of patients with NonSqNSCLC were predicted to have an oncogenic driver fusion identified by RNA, but not DNA CGP, according to a model that accounts for multiple real-world factors. Conclusion A well-designed DNA CGP assay is capable of robust fusion detection and these fusion calls are reliable for informing clinical decision-making. While DNA CGP detects most driver fusions, the clinical impact of fusion detection is substantial for individual patients and exhaustive efforts, inclusive of additional RNA-based testing, should be considered when an oncogenic driver is not clearly identified. [ABSTRACT FROM AUTHOR]

The use of biomarker testing to inform treatment decisions has emerged as a standard of care in multiple cancer types. However, the rates of patients with genomic testing results in hand to inform treatment decision-making remain variable. Here, we studied the impact of comprehensive genomic profiling (CGP) on clinical trial enrollment rates in patients with advanced-stage non-small cell lung, colorectal, breast, and prostate cancer using a real-world clinicogenomic database. On average, clinical trial enrollment in the therapy line immediately after CGP report receipt was 5.4%, which represents a 3.0 percentage point increase compared to therapy lines preceding CGP report receipt, supporting a meaningful association between CGP report availability and increased clinical trial enrollment., (© The Author(s) 2024. Published by Oxford University Press.)