9029 Background: Little data is available to guide clinical management of individuals with less common oncogenic drivers such as exon 18 mutations (ex18m) in EGFR. To better understand the impact of these rare mutations on treatment outcomes, we reviewed clinicopathologic data in patients (pts) with ex18m treated with tyrosine kinase inhibitors (TKI) in EGFR-mutant lung cancers. Methods: Pts with EGFR ex18m were detected via molecular diagnostics using Sequenom™, FoundationOne™ or MSK IMPACT™ NGS testing from 2003-2016. We reviewed their clinical data for molecular alterations in EGFR, treatment outcomes in response to TKI (time on treatment) and median overall survival (OS). Results: We identified mutations in EGFR ex18m in 63 pts. Median age at diagnosis was 68; 63% were women; 29% never smokers. Overall, 74 ex18m were found in 63 pts, including: G719A = 38, G719S = 11, G719C = 8, E709K = 6, E709_T710delinsD = 6, E709A = 3, G719D = 2. E709 and G719 co-mutations in ex18 were found in 9 pts, and 1 pt was found to have 3 separate tumors, each with a distinct ex18m. 29/63 (46%) patients with ex18m had a co-occurring EGFR mutation: 9 with another ex18m; 20 with ex19-21m. Using our IMPACT NGS, the median number of co-mutations was 8 (range 1-17). Two out of 63 pts had a pre-treatment T790M mutation. The 25 pts with non-metastatic disease presented in the following stages: IA = 19; IB = 3; IIB = 1; IIIA = 2; IIIB = 2. 34/38 pts with metastatic disease were treated with the following first-line EGFR-TKIs: erlotinib = 28, afatinib = 5, osimertinib = 1. Median duration on TKI treatment in months was: erlotinib = 10 mo, (range 1-25), afatinib = 3 mo (range 2-9), osimertinib = 4 mo. Median OS from the date of diagnosis of metastatic disease was 22 months (95% CI 18-29). In comparison, a similar cohort of pts with sensitizing EGFR exon19del/L858R mutations had a median OS of 31 months (95% CI 28-33) (Naidoo Cancer2015). Conclusions: Almost half of ex18m occur concurrently with another EGFR mutation. Overall, ex18m pts have a shorter median OS when compared to similar patient cohorts. EGFR-TKIs appear to be an effective treatment for pts with ex18m in EGFR-mutant lung cancers.