Background: Trastuzumab (T) plus chemotherapy is standard of care for pts with HER2+ adv GE cancer. Selection for T relies on HER2+ result by immunohistochemistry (IHC) +/- in-situ hybridization (ISH); ERBB2 amplification by comprehensive genomic profiling (CGP) also predicts benefit. As CGP use increases, it is important to explore associations of IHC/ISH and CGP result agreement with clinical outcomes in pts with adv GE cancer. Methods: Pts with adv GE cancer were selected from the Flatiron Health-Foundation Medicine (FMI) clinico-genomic database (CGDB), a nationwide de-identified EHR-derived clinical database linked to FMI genomic data. Pts treated from 01/2011-12/2018 with CGP data for tissue specimens collected before 1L were included. Agreement between HER2 status by IHC +/- ISH v ERBB2 amplification by CGP was assessed. For 1L containing T, time to tx discontinuation (TTD) and overall survival (OS) from 1L start stratified by HER2:ERBB2 agreement and ERBB2 copy number (CN) [ERBB2+ = CN >4] were estimated with unadjusted Kaplan-Meier analysis and adjusted (practice type, sex, age at adv dx) hazard ratios (aHR) from Cox proportional hazards models. Results: Of 596 HER2-tested pts with adv GE cancer in CGDB, 174 (29%) were HER2+ by IHC/ISH. Median age at adv dx was 63 y; 76.5% were male and 97% had adenocarcinoma. Overall HER2:ERBB2 agreement was 91%. Of 123 HER2+ 1L T-treated pts, median TTD and OS were longer for HER2+:ERBB2+ (concordant; n = 93) v HER2+:ERBB2- pts (discordant; n = 30): TTD, 5.2 v 0.8 months, aHR 0.46 (0.29-0.70); OS 14.8 v 7.5 months, aHR 0.38 (0.21-0.68). Median OS was 22.0 vs 8.4 months for 1L T-treated pts with ERBB2 CN > 30 (median) v CN ≤30 (aHR 0.69 [0.37-1.27]). Conclusions: In this large real-world clinico-genomic dataset, HER2:ERBB2 agreement was high in tested pts with adv GE cancer. 1L T-treated pts with discordant tests (HER2+:ERBB2-) had significantly shorter TTD and OS. Pts with higher ERBB2 CN had longer OS, but this finding was not significant after adjusting for covariates. Further research is needed to explore associations between HER2:ERBB2 agreement and clinical outcomes in this population.