Neoadjuvant with low-dose radiotherapy, tislelizumab, albumin-bound paclitaxel, and cisplatin for resectable locally advanced head and neck squamous cell carcinoma: phase II single-arm trial
Zhigang Liu, Dong Wang, Guanjun Li, Muhua Yi, Zhaoyuan Zhang, Guihua Zhong, Liangfu Xu, Rong Jiang, Yannan Zheng, Linxuan Huang, Yingpeng Peng, Yingpeng Peng, Jianpeng Li, Ye Liu, Jun Lai, Xiaofei Lv, Yongqiang Xu, Qiaodan Liu, Zhi‐Qiang Wang, Zhiqiang Wang, Qinan Yang, Li Nie, Lei Jiao, Xiaotao Huang, Jiao Lei, Wen Jiang, Zhi‐Jie Liu, Zhi‐Jie Liu, Wen Jiang
Abstract
Although pathological complete response (pCR) and major pathological response (MPR) rates of neoadjuvant immunotherapy combined with chemotherapy in head and neck squamous cell carcinoma (HNSCC) trials remain suboptimal, emerging evidence highlights the synergistic potential of combining low-dose radiotherapy with immunotherapy to promote the efficacy of immunotherapy. This phase II, open-label, single-arm, multicenter trial (NCT05343325) enrolled 28 patients with untreated stage III-IVB HNSCC (NeoRTPC02). Patients received neoadjuvant low-dose radiotherapy, the programmed death-1 (PD-1) inhibitor tislelizumab, albumin-bound paclitaxel, and cisplatin for two cycles, followed by radical resection ~4 weeks after treatment completion. The primary endpoint, pCR rate, was achieved in 14 of 23 patients (60.9%; 23/28, 82.1% of the total cohort underwent surgery). Secondary endpoints included MPR rate (21.7%, 5/23), R0 resection rate (100%), and objective response rate (64.3%; 18/28). Treatment-related adverse events were manageable, with grade 3 or 4 treatment-related adverse events occurring in 10 (35.7%) patients. No surgical delays were observed. Single-cell RNA sequencing revealed remodeling of the HNSCC tumor microenvironment, which may correlate with improved clinical outcomes. This trial met the pre-specified primary endpoint, demonstrating a high pCR rate with promising efficacy and manageable toxicity in locally advanced HNSCC. Neoadjuvant cancer therapeutic strategy has been explored in phase I/II clinical studies for head and neck squamous cell carcinoma. Here this group reports a single-arm, phase II clinical trial evaluating the neoadjuvant radiotherapy plus PD-1 inhibitor tislelizumab combined with paclitaxel and cisplatin, followed by radical surgical resection on 28 patients with untreated stage III-IVB head and neck squamous cell carcinoma.