e18101 Background: Treatment options for advanced R/M SGC are a limited and with variable response rates due to their safety/toxicity profile and the heterogenous l histology. Recent clinical trials tested pembrolizumab (PMB), a PD-1 inhibitor, in diverse settings. Methods: We performed a systematic review and single arm meta-analysis of clinical trials of PMB monotherapy or combined therapy in advanced and R/M SGC. PubMed, Scopus, and Cochrane database were searched for clinical trials published up to January 31, 2023. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. The primary endpoints of interest were complete/partial response (CR,PR) and disease control (DC= SD or better response) per RECIST v1.1, at any period of the trial. Results: Out of 199 database results, 4 clinical trials and 180 patients were included, all were using some form of PMB therapy. Overall, PMB was associated with a CR,PR ratio of 5.6% (95% CI 0.01-0.10, I²=25%, p=0.262) and DC ratio of 58.4% (95% CI 0.50-0.66, I²=13%, p=0.326), somewhat similar to recent evidence of PD-1/CTLA-4 combined therapy (nivolumab + ipilimumab [CR,PR=6-16%) in ongoing phase II clinical trials or PD-1 monotherapy (nivolumab [CR,PR=6%; SD=50%] in a completed clinical trial. Other systemic therapies, in which the current guidelines are based, include TKI (lenvatinib + sorafenib PR=3-15%; SD=50-94%) for adenoid cystic carcinoma (ACC); NTRK (larotrectinib CR,PR=90%, entrectinib CR,PR=86%), HER2 (transtuzumab associations CR,PR=60-90%), and AR (leuprorelin + bicalutamide CR,PR=42%, enzalutamide PR=4-15%; SD=52%) in non-ACC; and cytotoxic chemotherapy associations CR,PR=16-34% in heterogeneous histology tumors. Conclusions: There are marked limitations to the applicability of these findings in clinical practice, therefore a cautionary approach to this data is recommended, given their overall low statistical power, heterogenous histology, and tolerability to adverse effects. New trials with better standardized outcomes and comparative arms for different therapy associations and populations will help clarify the effects PD-1 inhibitors in the treatment of advanced and R/M SGC. [Table: see text]