Background: Next generation sequencing (NGS) of routinely fixed tissue from pts with advanced solid tumors may inform treatment planning. Foundation Medicine has developed a CLIA-certified, CAP-accredited test (FoundationOne, F1) to simultaneously characterize all 4 classes of genomic alterations in 236 (originally 182) cancer genes. Primary study objective was to determine how many physicians would change treatment approach based on F1 results (switch rate=SR). An exploratory objective was to compare PFS impact of any switches. Methods: This was a prospective, multicenter, single-arm trial in pts with refractory metastatic solid tumors of any type. Eligible pts must have been receiving second- or third-line therapy (first-line for pancreatic) and were initially registered within 10 weeks of beginning a regimen and before response assessment reimaging. Tumors were assayed with F1 after initial registration. Upon progression and documentation of next proposed therapy, they were re-registered and results of F1 were provided to doctors. If F1 caused a change in proposed therapy, a switch was recorded. Results: 233 pts were eligible; 103 were not re-registered (pt died, investigator decision, withdrew consent). Two questionnaires were missing; 128 pts were included in this analysis. Median age 61 yrs; female (65.6%). Tumor types mainly included breast (20%), lung (16%), and colon (13%). The SR was 28.1% (36 switch, 92 no switch). For 95 treated pts, the SR was 27.4% (26 received switch drug, 69 received initial recommendation; [33 pts did not receive Rx due to PD, death, hospice, or pt decision]). All of the major tumor types above had switch rates above 20%. In 77% of nonswitch cases, physicians reported that there were “not enough” treatment options available. Data collection for PFS analysis and correlation of results to tumor genomic profiles are ongoing. Conclusions: Comprehensive NGS-based profiling resulted in altered therapeutic choice in 28% of advanced solid tumor patients in the community setting, highlighting the current broad applicability of this approach. As more targeted therapeutics advance to larger trials and become approved, the impact of comprehensive testing may be expected to increase.