Oral fluoropyrimidines as alternatives to intravenous 5-fluorouracil in combination with immune checkpoint inhibitors for recurrent metastatic head neck squamous cell carcinoma.

e18015 Background: Based on the KEYNOTE-048 trial, immune checkpoint inhibitors (ICIs) with or without chemotherapy have become the new standard for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Although pembrolizumab combined with chemotherapy—including continuous intravenous 5-fluorouracil (5-FU)—achieves higher response rates than pembrolizumab alone, prolonged hospitalization and adverse events make this regimen challenging to implement in real-world practice. Whether oral fluoropyrimidines can replace continuous 5-FU warrants further investigation. This study evaluated the efficacy of ICIs plus platinum and oral tegafur-uracil as first-line therapy for R/M HNSCC. Methods: This single-institution retrospective cohort study enrolled patients receiving ICIs combined with platinum and fluoropyrimidine-based therapy as first-line treatment. Patients were stratified according to the route of fluoropyrimidine administration: oral tegafur-uracil versus intravenous 5-FU. Propensity score matching was employed to balance baseline characteristics and pretreatment biochemical parameters. Progression-free survival (PFS) and overall survival (OS) were analysed. Results: Among 116 patients, 20.7% (N = 24) received oral therapy. Before matching, no statistically significant differences in survival were observed between groups, although outcomes numerically favored the oral cohort (PFS: 5.3 vs. 6.4 months, HR [95% CI]: 0.979 [0.524–1.829]; OS: not reached vs. 11.0 months, HR [95% CI]: 0.415 [0.165–1.309]). Recurrent T staging and neutrophil-lymphocyte ratio were independent prognostic factors for OS, with HRs [95% CIs] of 2.181 [1.276–3.726] and 2.268 [1.276–3.726], respectively. Patients with distant metastases and higher neutrophil-monocyte ratios demonstrated a superior survival benefit with oral therapy (Table 1). After 1:2 propensity score matching, survival trends persisted (PFS: 5.3 vs. 6.3 months; HR [95% CI]: 1.515 [0.619–3.712]; OS: not reached vs. 11.2 months; HR [95% CI]: 0.465 [0.133–1.619]). Conclusions: Oral tegafur-uracil demonstrated non-inferior outcomes compared to continuous intravenous 5-FU when combined with ICIs for R/M HNSCC. Prospective randomized controlled trials are warranted to confirm these findings. Hazard ratio between patients with or without oral tegafur-uracil for survival outcomes. PFS (HR, 95% CI) OS (HR, 95% CI) Distant metastasis Yes 0.618 (0.206-1.855) 0.145 (0.019-1.083) No 1.233 (0.574-2.653) 0.682 (0.240-1.937) Neutrophil-monocyte ratio Higher 0.510 (0.196-1.324) 0.189 (0.045-0.793) Lower 2.027 (0.860-4.776) 0.949 (0.279-3.236) All patients 0.979 (0.524-1.829) 0.415 (0.165-1.039)