e18118 Background: Precision oncology – use of tumor genomic profiling to guide therapies – is widely discussed but with limited real-world data. We have previously reported our prospective study on feasibility and clinical utility of routine somatic genomic testing of solid tumors [ J Natl Cancer Inst. 2015; 108(3)], and here we report our longitudinal experience, focusing on therapeutic impact. Methods: Records were reviewed for consecutive adult patients seen at Cleveland Clinic for a solid tumor malignancy without known curative options where tumor genomic profiling was ordered using FoundationOne™ (Cambridge, MA). Results were discussed at the Cleveland Clinic Genomics Tumor Board, and therapeutic recommendations were conveyed to the primary oncologist. Data for this cohort study approved by the Cleveland Clinic IRB included subsequent therapies and clinical outcomes. Results: From 2013 to 2016, 330 patients had tumor genomic testing ordered. Median age was 61 years (range, 24-94); 170 (51.5%) were female; 289 (87.6%) were Caucasian. Colorectal (21.5%), breast (17%), lung (16.1%), and pancreatobiliary (11.5%) cancers were the most common diagnoses. In 300 resulted cases, a median of 4 (0-20) alterations per specimen were noted; the most commonly altered genes were TP53 (n = 174), KRAS (n = 75), APC (n = 65), CDKN2A/B (n = 49), and PIK3CA/ PIK3R (n = 46). A specific therapy targeting an actionable alteration was recommended in 51% (153/300) of patients, and 11.7% (n = 35) received such therapy: 14 on clinical trials, 5 on-label, and 16 off-label. Most common targets for therapy were PIK3CA/PIK3R/PTEN (n = 7), HER2 (6), BRAF (3), EGFR (3), and ALK, FLT3, NTRK1 and RET (2 each). At last follow-up, of 35 patients receiving targeted therapy, best responses were: complete response (n = 1, 2.9%), partial response (n = 5, 14.3%), stable disease (n = 14, 40%), progressive disease (n = 11, 31.4%); data not available for 4 patients. Non-availability of clinical trials was a common reason for non-receipt of targeted therapy. Conclusions: Tumor genomic profiling influenced treatment in 11.7% of patients in this cohort, and 57% of those receiving targeted therapy experienced clinical benefit. These data can help guide real-world discussions of precision oncology.