An exploratory study of nimotuzumab combined with toripalimab and chemotherapy for locally advanced tonsillar cancer.

Background: Neoadjuvant immunotherapy/targeted therapy combined with chemotherapy shows encouraging activity for oropharyngeal squamous cell carcinoma (OPSCC). However, evidence specific to tonsillar squamous cell carcinoma (TSCC) remains limited, particularly regarding the systematic relationships among radiological response, pathologic response, margin control, and voice and swallowing functional outcomes. Methods: This single-arm, single-center study included patients with pathologically confirmed TSCC diagnosed between January 2024 and June 2025. Patients received triplet neoadjuvant therapy consisting of nimotuzumab, toripalimab, nab-paclitaxel, and carboplatin every 3 weeks for 2 cycles, followed by transoral radical tonsillectomy combined with radical cervical lymph node dissection. Radiologic response was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and volumetric magnetic resonance imaging (MRI). Pathologic response, margin status, perioperative safety, adjuvant treatment, and functional outcomes were evaluated. Results: Twenty patients achieved clinicopathologic downstaging after surgery. The primary-site pCR rate was 65.0%, nodal pCR was 60.0%, and overall ypT0N0 pCR was 45.0%. The objective radiological response (ORR) rate of the primary lesion was 100%, and 9 patients (45%) achieved a complete radiological response. Mean primary-tumor and dominant-node volume reductions were 76.18% and 72.59%, respectively. Both pre- and postneoadjuvant margins were negative in all patients, yielding R0 resection in all cases. Functional scores improved after neoadjuvant therapy, worsened transiently during radiotherapy, and generally recovered during follow-up. Conclusions: Nimotuzumab plus toripalimab and chemotherapy produced high radiological and pathological response rates with reliable margin control in patients with locally advanced TSCC. Postneoadjuvant boundary assessment with intraoperative pathologic verification may support individualized resection planning, but routine resection of the primary lesion and cervical lymph node dissection remain necessary. Longer follow-up and prospective validation are required to confirm these results. Clinical trial registration: https://clinicaltrials.gov/study/, identifier NCT07353723.