Mandibular preservation with neoadjuvant tislelizumab plus platinum-doublet chemotherapy in locally advanced resectable oral squamous cell carcinoma: A prospective phase II trial.

Abstract

6090 Background: Segmental mandibulectomy for locally advanced oral squamous cell carcinoma (OSCC) severely compromises quality of life. In patients without radiographic mandibular invasion but still requiring mandibulectomy to achieve negative margins, effective tumor downstaging strategies that enable mandibular preservation are of major clinical importance. Neoadjuvant chemo-immunotherapy may reduce tumor burden, potentially enabling less radical resection and mandibular preservation. This study aimed to evaluate the efficacy and safety of mandibular preservation using neoadjuvant tislelizumab plus platinum-doublet chemotherapy in resectable locally advanced OSCC. Methods: This phase II, open-label, single-arm trial enrolled previously untreated patients with locally advanced, resectable OSCC (stage III-IVB, T3-T4N0-3M0) necessitating mandibulectomy based on conventional surgical criteria despite the absence of definitive clinicoradiologic mandibular invasion. Neoadjuvant treatment consisted of tislelizumab (200 mg), docetaxel (75 mg/m 2 ) and cisplatin (60 mg/m 2 ) on day 1 of each 21-day cycle for three cycles. All patients then proceeded to surgery. The primary endpoint was mandibular preservation rate. Secondary endpoints included pathological complete response (pCR), major pathological response (MPR), margin-negative resection (R0) rate, objective response rate (ORR), progression-free survival, disease-free survival, overall survival and treatment-related adverse events (TRAEs). Results: Between October 2023 and September 2025, a total of 53 patients were enrolled, and 49 were evaluable. All 49 patients completed three cycles of neoadjuvant therapy and underwent surgery. The mandibular preservation rate was 95.9% (47/49), and all patients achieved R0 resection. The ORR was 79.6% (39/49) and the pCR rate was 51.0% (25/49). TRAEs occurred in 100% (49/49) of patients. Grade 3 TRAEs were reported in 10.2% (5/49), including leukopenia, fatigue, and hypertension. No grade 4–5 TRAEs were observed. Conclusions: Neoadjuvant tislelizumab combined with platinum-doublet chemotherapy achieved a high mandibular preservation rate and a favorable pathological response profile with manageable toxicity in patients with locally advanced, resectable OSCC. This strategy represents a promising organ-preserving approach. Longer follow-up is ongoing to determine long-term survival outcomes. Clinical trial information: NCT06130007 .