Preoperative Chemoimmunotherapy followed by salvage surgery and adjuvant tislelizumab for previously irradiated R HNSCC: A prospective, phase II trial.

Abstract

The outcomes of salvage surgery for previously irradiated recurrent head and neck squamous cell carcinoma (HNSCC) remain suboptimal. This phase II trial evaluated the effects of preoperative tislelizumab (an anti-PD-1 monoclonal immunoglobulin G4 antibody) plus chemotherapy followed by salvage surgery and adjuvant tislelizumab in this setting. Eligible patients (n=34) with resectable recurrent HNSCC after radiotherapy received preoperative tislelizumab (200 mg), albumin-bound paclitaxel (260 mg/m²), and cisplatin (60-75 mg/m²) every 3 weeks for 2 cycles, followed by salvage surgery and 6 cycles of adjuvant tislelizumab. The primary endpoint was major pathological response (MPR). Secondary endpoints included pathological complete response (pCR), the objective response rate (ORR), 2-year event-free survival (EFS), 2-year overall survival (OS), and safety. The ORR was 35.3% (12/34). Of 26 surgical patients, R0 resection was achieved in 19 (73.1%). MPR rate was 19.2% (5/26), with a pCR rate of 15.4% (4/26). At median follow-up of 32 months, 2-year EFS was 39.6% and 2-year OS was 54.8%. All MPR patients remained disease-free. Grade 1-2 adverse events were common; one grade 3 hyperglycemia occurred. High baseline BCR repertoire diversity and clonal abundance (top 1%/10%) correlated with poor prognosis, with top 1% clonality showing strong prognostic power (AUC=0.910, p=0.006). Preoperative chemoimmunotherapy followed by surgery and adjuvant immunotherapy was feasible with encouraging survival in previously irradiated recurrent HNSCC. Baseline BCR repertoire characteristics may serve as a noninvasive prognostic biomarker.