e17582 Background: Salivary gland cancers (SGCs) are rare tumors. The approach to recurrent or metastatic patients is histology dependent, as the clinical course is highly variable. Response rates to chemotherapy are modest and no second-line therapies have proven to be effective. The rarity and heterogeneity of SGCs make conducting clinical trials challenging. Recent reports of Next Generation Sequencing (NGS) in SGCs have identified unique genetic attributes of certain histological classes. However, despite the elaborate work done with genetic characterization, there is very little evidence on whether these findings translate to tumor control. In this study, we aimed to explore the treatment outcomes of patients with advanced SGCs who underwent a commercially available NGS. Methods: A retrospective analysis of all patients with histologically confirmed SGC treated in three major Israeli cancer centers who underwent NGS. Results: Twenty-seven patients were included. Eighteen patients were male (66.6%). The median age was 59 (range 38-81). Histologic type was adenoid cystic carcinoma in 11 (40.7%) patients, 8 (29.6%) mucoepidermoid carcinomas, 5 (18.5%) adenocarcinomas, 2 (7.4%) salivary duct carcinomas and 1 (3.7%) acinic cell carcinoma. Twenty-five (92.6%) had recurrent disease after initial curative treatment and 2 were initially diagnosed with metastatic disease. Median time to recurrence was 24.3 months. The median number of systemic treatment lines was 1 (range 0-5). Thirteen patients (48%) had targetable findings in NGS, including: 5 ERBB2 amplifications, 3 PIK3CA mutation, 1 TRIM33-RET fusion, 1 FGFR3-TACC3 fusion, 1 MSI-high and 2 high mutational burden. Nine patients were treated accordingly; 5 in the second-line and 4 as first-line treatment. Median progression-free survival for targeted treatment was 8.4 months. Of 4 patients who achieved durable responses to anti-RET/HER2 agents and immunotherapy of 8.4 – 31.1 months, two are ongoing. The median overall survival for all patients was 101.75 months, was not reached for patients receiving targeted treatment and was 40.4 months for patients treated conventionally (p = 0.26). Conclusions: In the absence of a well-established therapeutic approach, NGS may detect clinically significant genetic alterations and benefit patients with advanced SGCs.