A Phase II Trial of Neoadjuvant Albumin-Bound Paclitaxel Plus Carboplatin Combined with Tislelizumab in Locally Advanced HNSCC: Efficacy and Biomarker Exploration.

Abstract Purpose: This study was to evaluate the efficacy of neoadjuvant chemotherapy combined with the PD-1 inhibitor tislelizumab in patients with potentially resectable stage II-IVb head and neck squamous cell carcinoma (HNSCC) and to explore immune and circulating tumor–related features potentially associated with treatment response. Patients and Methods: This was a single-arm phase II trial involving 33 patients with potentially resectable stage II–IVb HNSCC. Participants received two cycles of neoadjuvant therapy followed by surgery. Primary endpoints were pathological complete response (pCR) rate and major pathological response (MPR) rate. Safety and exploratory analyses, including circulating tumor cells (CTCs), PD-L1 expression, and T-cell senescence, were also assessed. Results: The study demonstrated an objective response rate of 72.7% (24/33) and an R0 resection rate of 93.1% (27/29) in surgical patients. The pCR rate was 44.8%, and the MPR rate was 62.1%. The laryngeal preservation rate was 70.4% (19/27). With a median follow-up of 20.5 months, the 12- and 24-month event-free survival rates were 93.1%. 5 of 6 patients with decreased CTC levels achieved MPR. Among patients whose T cell senescence decreased, 4 out of 6 achieved MPR, whereas only 2 out of 5 with increased T cell senescence achieved MPR. The pCR rate was significantly higher in patients with PD-L1 CPS≥1 compared to those with CPS<1. Conclusions: Neoadjuvant immunochemotherapy improves pathological response and organ preservation. Dynamic changes in CTCs and T-cell senescence are associated with treatment efficacy, suggesting their potential as early, non-invasive indicators of response, supporting precision treatment strategies for locally advanced HNSCC.