Madison R, Schrock AB, Castellanos E, et al. - Given the increasing use of liquid biopsy and comprehensive genomic profiling (CGP) of circulating tumor DNA (ctDNA) for finding targetable genomic alterations (GA) in non-small cell lung cancer (NSCLC), researchers here investigated clinical outcomes for patients after CGP using liquid biopsy vs tissue biopsy, getting matched targeted therapy after CGP, and associated outcomes in the real-world setting. They included 6,491 patients with NSCLC and liquid biopsy (N = 937 tests) and/or tissue (N = 5,582 tests) CGP in a de-identified commercial clinico-genomic database. National Comprehensive Cancer Network NSCLC guideline biomarkers were among the targetable GAs. Retrospective analysis of real-world clinico-genomic data revealed comparable clinical outcomes on matched targeted therapy after liquid biopsy and tissue CGP in NSCLC. This suggests therapy selection can be reliably guided by routine clinical use of liquid biopsy CGP.