e15036 Background: Advances in tumor molecular profiling and bioinformatics are adding new insights to support real-world research. In this study, paired tumor NGS testing data was curated and analyzed from electronic medical records (EMR) to understand mutational and targeted therapy landscape. Methods: A database initiated in 2013 to collect data, including outcomes, on all patients referred to the molecular tumor board at the Avera Cancer Institute was curated and analyzed. A data pipeline that combined results from curated NGS data with curated EMR data from Avera was used to correlate targetable mutations to a corresponding therapy and assessed treatment patterns. Results: Data were from 1804 patients with 44 cancer types including breast (462; 26%), lung (338;19%), colorectal (198;11%), ovarian (168;9%), and uterine (100;5%). Overall, 83% of patients had a positive NGS result and 67% had a targetable mutation per NCCN guidelines. 32% of patients with a targetable mutation received targeted therapy per guideline. Overall, 381 patients with 28 tumor types received targeted therapies based on NGS results and targetable biomarkers. Of these, 288/381 (76%) were stage III-IV and 93/381 (24%) early stage/stage unknown. In non-small cell lung cancer, 76% of stage III-IV patients with mutations in EGFR (exon 19 deletion, L858, L861, S768, G719), MET (exon 14 skipping, amplification), BRAF V600 and ALK/ ROS1/ RET fusions received a targeted therapy per NCCN guidelines. In advanced breast cancer, 97% with ERBB2 amplification received targeted therapy (trastuzumab, pertuzumab, neratinib, lapatinib, tucatinib). 8% of advanced breast cancer patients with PIK3CA mutation received alpelisib, with all patients receiving the drug since 2019. 38% advanced breast cancer patients with BRCA1/2 mutation received Olaparib. In ovarian cancer, 48% of advanced stage patients received targeted therapy for BRCA 1/2, ATM, CDK12, CHEK2, ERBB2, FANCL, KRAS, ALK, BRAF alterations. Olaparib was used in 70% of advanced prostate cancer patients with BRCA1/2 mutations. Dabrafenib combined with Trametinib were most preferred for BRAF V600 mutation in melanoma and colorectal tumors respectively. Off label use of targeted therapy was observed in about 6% of advanced patients; examples include trametinib for KRAS/NRAS mutation [non-small cell lung cancer, colorectal, pancreatic, ovarian], PARP inhibitors for BRCA1/2, ATM mutations [urothelial, peritoneal], anti-ERBB2 inhibitors for ERBB2 in-frame, missense, exon 20 insertion mutations [lung and breast]. Conclusions: These study results demonstrate that automated data mining can provide insights into the genomic and therapeutic landscape of a real-world patient population. Across all tumor types, most patients are being given appropriate targeted therapies as per guidelines. Off-label use of targeted therapy was also observed.