Survival outcomes with contemporary treatments including immunotherapy for poorly differentiated neuroendocrine carcinomas of the head and neck.

6115 Background: Poorly differentiated Neuroendocrine Carcinomas of the Head and Neck (HN-NECs) are rare aggressive malignancies with limited data guiding therapeutic approaches, particularly in the metastatic setting, with cytotoxic chemotherapy (chemo) comprising the backbone of management. Despite the widespread use of immune checkpoint inhibitors/immunotherapy (IO) in advanced lung NECs, evidence regarding their utility in the extrapulmonary setting, particularly for HN-NECs, is scarce. We explored real-world outcomes with various therapeutic strategies, including IO, in patients with metastatic HN-NECs, using the National Cancer Database (NCDB). Methods: Patients with metastatic HN-NECs diagnosed between 2018 to 2023 were identified. Overall survival (OS) was analyzed using Kaplan-Meier estimations and Cox proportional hazards regression. Results: A total of 275 patients with metastatic HN-NECs were identified. Primary sites included larynx (n = 75, 27.3%), pharynx (n = 72, 26.2%), nasal cavity + paranasal sinuses (n = 67, 24.4%), and oral cavity (n = 61, 22.2%). Most common metastatic sites were liver (n = 128, 46.5%) and bone (N = 272; n = 116, 42.6%). Of these 275 patients, 212 (77.1%) received chemo, 95 (34.5%) received IO, 122 (44.4%) received radiotherapy (RT), and 46 (16.7%) underwent primary site surgery (surg). Among patients with available survival data (N = 227), receipt of chemo (n = 174) and/or IO (n = 78) were associated with prolonged OS vs. no chemo (p <0.001) and/or no IO (p = 0.005), respectively. Use of RT (n = 105; p = 0.17) and surg (n = 39; p = 0.18) were not significantly associated with OS (Table). Among 174 patients who received chemo, concurrent IO (chemoIO; n = 73) was associated with significantly prolonged OS vs. chemo alone (14.1 months [m] vs. 9.9 m; HR, 0.67; 95% CI, 0.47 – 0.96; p = 0.03). On multivariable analysis adjusting for bone metastatic disease (the only other significant prognostic covariate on univariable regression), chemoIO remained associated with reduced mortality risk vs. chemo alone (HR 0.57; 95% CI, 0.39 – 0.82; p = 0.003). Conclusions: Akin to lung NECs, IO may improve OS in HN-NECs. Despite NCDB limitations, chemoIO was associated with prolonged OS over chemo alone. Further prospective evaluations are warranted, and results from ongoing studies (e.g., NCT05058651) are awaited. Survival comparisons with univariable Cox proportional hazards regression. Treatment Group Median OS in months (95% CI) HR (95% CI) p Chemo (vs. No Chemo) 11.3 (9.5 – 14.2) vs. 3.4 (2.7 – 6.2) 0.53 (0.38 – 0.74) <0.001 IO (vs. No IO) 13.0 (10.8 – 17.1) vs. 8.1 (6.2 – 10.3) 0.63 (0.46 – 0.87) 0.005 RT (vs. No RT) 10.8 (8.8 – 14.6) vs. 8.5 (6.4 – 11.7) 0.81 (0.60 – 1.09) 0.17 Primary Site Surgery (vs. No Surgery) 12.5 (8.7 – 28.5) vs. 9.0 (7.7 – 11.7) 0.76 (0.51 – 1.14) 0.18 ChemoIO (vs. Chemo alone) 14.1 (11.1 – 19.3) vs. 9.9 (8.3 – 13.7) 0.67 (0.47 – 0.96) 0.03