Abstract
BACKGROUND: PD-1 inhibitors are first-line treatments for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, previous trials included few participants from mainland China and other Asian regions and differed from real-world practice. PD-L1 expression alone has limited predictive value. This study aimed to systematically evaluate efficacy and survival differences in diverse clinical scenarios and identify associated peripheral blood markers (PBMs). METHODS: Data were retrospectively collected from 105 R/M HNSCC patients treated with first-line immunotherapy alone or in combination across 3 hospitals in China (2020.01-2022.12). Primary endpoints were overall survival (OS) and progression-free survival (PFS). We assessed efficacy, survival, and safety, and developed predictive models. Data analyses were performed using SPSS 26.0 and GraphPad Prism 8.0.1. RESULTS: The median follow-up was 21 months. The objective response rate was 37.14%. Median OS was 21 months (1-year OS: 81.02%), and median PFS was 11 months (1-year PFS: 39.47%). Immunotherapy was more effective for distant metastasis (DM) than local recurrence (LR). For patients with LR, DM, or both, median PFS was 12, 14, and 7.5 months, respectively (P = 0.0029). Higher combined positive score (CPS) predicted better outcomes. Median OS for CPS ≥ 20, 1 ≤ CPS < 20, and CPS < 1 was 32, 20, and 12 months, respectively (P = 0.0008). In the comparison of combination versus single-agent immunotherapy, median PFS was 12 versus 9 months (P = 0.0044). Combining taxanes with immunotherapy yielded favorable results, with a median OS of 27 months. No survival difference was found between domestic and imported PD-1 inhibitors. Secondary radiotherapy did not improve survival. Increased peripheral blood lymphocyte subsets and decreased peripheral blood inflammatory markers were associated with superior immunotherapy outcomes. Key predictive PBMs included baseline CD8(+) T cells, CD3(+) T cells at 12 weeks post-treatment (12w pt), CD4(+) T cells at 6w pt, and CD8(+) T cells at 12w pt. CONCLUSION: This study focused on evaluating immunotherapy efficacy and survival differences in R/M HNSCC patients across various clinical background. Dynamic PBMs correlated closely with immunotherapy response and survival prognosis. These findings expanded treatment options and supported personalized decisions. R/M HNSCC, Immunotherapy, Real-world study, Efficacy and survival differences, Predictive markers.