e18728 Background: The R/M HNSCC treatment landscape has evolved significantly in recent years, notably with the approval of 2 immuno-oncology agents (IO), pembrolizumab (second-line [2L] approval, 2016; first-line [1L] approval, 2019) and nivolumab (2L approval, 2016). Review of the literature suggests there is limited real-world (rw) data on clinical outcomes and safety associated with chemotherapy (chemo) and IO in R/M HNSCC. These analyses present a review of patient charts to assess rw clinical outcomes and safety in R/M HNSCC, stratified by patient factors. Methods: Data were derived via structured data extraction and manual review of electronic health records (EHRs; January 1, 2016–December 31, 2019) for patients with R/M HNSCC and who initiated systemic treatment at a community oncology practice in The US Oncology Network. Time-to-event endpoints were assessed by unadjusted Kaplan–Meier analyses and included death (rw overall survival [OS]), provider-assessed progression (rw progression-free survival [PFS]), rw duration of response (DoR), and treatment discontinuation (rw time-to-discontinuation [TTD]). Treatment sequences were evaluated following R/M HNSCC diagnosis. Provider-assessed response rates and adverse events (AEs) as captured in the EHRs were reported. Results: Overall, 257 patients who received 1L treatment were included in these analyses; median age was 64 years (range: 21, 90+); the majority of patients were male (77.4%) and white (74.7%), and 17.5% had evaluable PD-L1 status. The most common 1L treatment regimens were nivolumab (18.3%), carboplatin + paclitaxel (16.0%), and pembrolizumab (14.8%). Median follow-up time from treatment initiation was 7.9 months (range: 0.2, 45.9). Of the 174 patients with evaluable response to 1L treatment, overall response rate was 48.5% (95% CI: 38.3, 58.8) for chemo and 40.0% (95% CI: 28.9, 52.0) for IO. Median rwDoR was 7.6 months (95% CI: 5.8, 11.2). Median rwOS was 12.1 months (95% CI: 10.5, 16.6), and median rwPFS was 5.9 months (95% CI: 4.7, 6.8). Median rwTTD was 2.3 months (95% CI: 2.0, 3.2). The top reason for treatment discontinuation was treatment completion (38.5%) for chemo and progression (46.6.%) for IO. The most commonly reported AEs were rash (17.5%), fatigue (14.4%), and nausea (14.4%) for chemo and fatigue (12.4%), rash (7.2%), and anemia (5.2%) for IO. The percentage of AEs that did not require any intervention was 34.4% for chemo and 20.6% for IO. Conclusions: These analyses present rw clinical outcomes for patients with R/M HNSCC in community oncology practices. The proven role of IO continues to evolve, and continued work is needed to best demarcate the use of these agents, in addition to exploration of additional therapeutics for use in R/M HNSCC. Study funding: GlaxoSmithKline (GSK Study 207139).