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

Abstract

The aim of this study was to evaluate the efficacy of neoadjuvant chemotherapy (albumin-bound paclitaxel + carboplatin) combined with the PD-1 inhibitor tislelizumab in patients with potentially resectable stage II to IVb head and neck squamous cell carcinoma (HNSCC) and explore immune and circulating tumor-related features potentially associated with treatment response. This was a single-arm phase II trial involving 33 patients with potentially resectable stage II to IVb HNSCC. Participants received two cycles of neoadjuvant therapy followed by surgery. Primary endpoints were pathologic complete response (pCR) rate and major pathologic response (MPR) rate. Safety and exploratory analyses, including circulating tumor cells (CTC), PD-L1 expression, and T-cell senescence, were also assessed. 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% (95% confidence interval, 84.3%-100%). Five of six patients with decreased CTC levels achieved MPR (5/6, 83.3%). Among patients whose T-cell senescence decreased, four of six achieved MPR, whereas only two of five with increased T-cell senescence achieved MPR. The pCR rate was significantly higher in patients with PD-L1 combined positive score ≥ 1 compared with those with combined positive score < 1 (55.6% vs. 12.5%). Neoadjuvant immunochemotherapy improves pathologic response and organ preservation in stage II to IVb HNSCC. Dynamic changes in CTCs and T-cell senescence are associated with treatment efficacy, suggesting their potential as early, noninvasive indicators of response, supporting precision treatment strategies for locally advanced HNSCC.