Tislelizumab in combination with carboplatin and albumin–binding paclitaxel for neoadjuvant therapy in head and neck squamous cell carcinoma: A prospective, phase II clinical study.

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Background: Surgery followed by adjuvant therapy remains the standard treatment for locally advanced head and neck squamous cell carcinoma (LA–HNSCC). Neoadjuvant chemotherapy alone has not improved survival. Although perioperative immunotherapy has been approved based on the KEYNOTE–689 trial, pathological response and event–free survival (EFS) remain modest. Immunotherapy combined with chemotherapy may enhance antitumor efficacy, but prospective evidence remains limited. Methods: This single–center, prospective, single–arm phase II trial (NCT05941338) enrolled 100 treatment–naïve patients with resectable stage III–IVA (AJCC 8th edition) HNSCC. Patients received two cycles of neoadjuvant tislelizumab (200 mg Q3W), carboplatin (AUC 5), and albumin–bound paclitaxel (260 mg/m²), followed by surgery and risk–adapted adjuvant therapy. Primary endpoints were major pathological response (MPR; ≤10% residual viable tumor) and serious adverse events. Secondary endpoints included EFS, overall survival (OS), pathological complete response (pCR), radiological response, and surgical feasibility. Results: Ninety–five patients (95.0%) underwent definitive surgery. The objective radiological response rate was 83.0%. Pathological assessment showed an MPR rate of 57.9%, including pCR in some patients. No treatment–related surgical delays or deaths occurred. Grade 3–4 treatment–related adverse events occurred in 8%. At a median follow–up of 23.8 months, 12–month EFS and OS rates were 90.5% and 98.9%, respectively. Patients achieving MPR had significantly superior EFS compared with non–MPR patients (12–month EFS: 98.1% vs. 80.0%; P = 0.001; HR 0.072). Postoperative adjuvant modality was not associated with EFS. In contrast, baseline lymph node positivity, ypN2–3 disease, extranodal extension, and advanced pathological T stage were significantly associated with inferior EFS. Conclusions: Neoadjuvant tislelizumab combined with carboplatin and albumin–bound paclitaxel demonstrated favorable safety, a high MPR rate, and encouraging short–term EFS in resectable LA–HNSCC. MPR was strongly associated with postoperative EFS, supporting its potential role as an early surrogate endpoint. Pathological risk stratification may guide individualized adjuvant therapy, enabling treatment de–escalation in low–risk patients and intensification in high–risk populations. Clinical trial information: NCT05941338 .