| Description |
Routine KRAS mutations testing in metastatic colorectal cancer (CRC) patients to guide anti-EGFR-targeted therapy use is recommended by clinical guidelines. CRC patients may have mutations in other KRAS sites not routinely tested, and in other potentially chemotherapy targetable genes. Multigene genomic profiling can identify mutations at a relatively reasonable cost, but its clinical utility has never been reported. This research’s goal was to compare clinical utility measures of multigene genomic profiling in metastatic CRC patients to measures associated with KRAS single gene testing. The research hypothesis was higher clinical utility associated with multigene genomic profiling, leading to more appropriate use of targeted therapies, more clinical trial enrollment, and improved survival compared to KRAS single gene testing. An observational study of genomically-tested adult metastatic CRC patients who were alive between 06/01/2008-01/20/2016 and treated at the Huntsman Cancer Institute (HCI) was conducted. A comprehensive database was created combining data from HCI tumor registry, ARUP laboratories, UUHC EDW, and Oncore database. Index date was metastatic CRC diagnosis date. First, a cross-sectional study classified mutations detected by multigene genomic profiling into: actionable, potentially actionable, and nonactionable at patient and mutation level. Then, a retrospective cohort study compared treatment decisions and overall survival of multigene genomically profiled patients to those tested with KRAS single gene testing only. Baseline clinical and tumor characteristics were compared and included in regression analyses. Of 2,351 patients identified in the colorectal cohort, only 474 met eligibility criteria: 162 patients had KRAS single gene testing and 312 had multigene genomic profiling. Multigene genomic profiling identified multiple mutations of unknown significance that cannot guide evidence-based treatment decisions. However, the majority of patients had at least 1 mutation that offered potential investigational treatment options. Compared to KRAS single gene testing, multigene genomic profiling was not associated with more appropriate use of targeted therapy or overall survival difference, but was associated with significant increase in clinical trial enrollment. In conclusion, the value of this additional genetic information is still questionable. While multigene genomic profiling offers more trial enrollment and may inform future treatment decisions, currently multigene genomic profiling is not resulting in improved outcomes in metastatic CRC patients. |
