Efficacy of Tirellizumab Combined With TP Neoadjuvant Therapy in the Treatment of Early Oral Squamous Cell Carcinoma (cT1-2N0M0) Versus Standard Therapy: a Randomized Controlled, Single-center Exploratory Clinical Study

oral squamous cell carcinoma (OSCC) is one of the most common cancers in the world, with about 900,000 new cases and 500,000 deaths in 2020, of which about 30-40% are early stage cancers [1, 2]. According to the 2024 NCCN guidelines and 2023 CSCO guidelines, surgery is the main treatment for early oral cancer, and patients with high-risk factors receive adjuvant radiotherapy and chemotherapy after surgery. It has been reported in literature that the 5-year OS of early stage (T1-2N0M0) OSCC is 75.8% [3], among which the 5-year OS of T2N0 OSCC patients is only 72%. The 2-year DFS is only 72%[4]. Clinical studies have shown that the 5-year survival rate of stage I and II in breast cancer patients is 99.2% and 93.1% respectively, while the 5-year survival rate of early lung cancer can reach more than 92% [5]. In comparison, the 5-year survival rate of early oral cancer (cT1-T2) is greatly reduced. Therefore, it is necessary to explore new therapeutic modalities to improve the prognosis of cT1-2N0M0 oral cancer.

With the rise of immunotherapy, patients with advanced head and neck squamous cell cancer are also benefiting. Antibodies to PD-1 or PD-L1 have demonstrated clear anti-tumor activity and safety in multiple cancer types, including melanoma, lung cancer, and head and neck cancer [6, 7]. In both first-line and second-line therapies for oral cancer, Nivolumab (PD-1 inhibitor) and Pembrolizumab (PD-1 inhibitor) have achieved good clinical efficacy, with response rates of 13.3% and 16.4% in Phase II clinical studies, respectively [7,8]. Multiple studies have shown that compared with advanced tumors, early tumors have smaller tumor load and heterogeneity, lower systemic immunosuppression, and more tumor-related T cell infiltration, and PD-1 inhibitors can achieve a higher response rate in neoadjuvant therapy for early solid tumors than for advanced tumors [9-11]. Although there is a lack of research on immunotherapy for early oral cancer, PD-1 inhibitors show good effects in early lung cancer and early triple-negative breast cancer, and EFS is significantly improved [12,13].

Data from our study showed that in 104 patients who received preoperative PD1 monoclonal antibody combined with chemotherapy neoadjuvant therapy, the postoperative pathological complete response (pCR) rate was 47.1%, and the major pathological response (MPR) rate was 65.4% (Figure 1). The 2-year estimated DFS rates were 89.7% and 75.51%, respectively, in the neoadjuvant and conventional surgical treatment cohort, while the 2-year estimated OS rates were 94.5% and 81.2%, respectively (Figure 2).

Figure 1 Postoperative pathological remission of the neoadjuvant exemption cohort FIG. 2 Prognosis of neoadjuvant immunity cohort compared with conventional surgery

Tirellizumab is a humanized IgG4 monoclonal antibody against PD-1, which has high affinity and binding specificity for PD-1. Its modification of Fc segment reduces the antigen-clearing effect of macrophages induced by mediated immune cell crosslinking, and enhances anti-tumor activity. The efficacy of Tirelizumab against tumors has been proven in the treatment of a variety of solid tumors, and its Disease control rate (DCR) can reach 50-80%[14,15]. As a uniquely modified PD-1 inhibitor, Tirellizumab may be safer and more effective in oral cancer. Paclitaxel combined with carboplatin is the first-line protocol for the treatment of recurrent or metastatic oral and oropharyngeal squamous cell carcinoma, and the induction chemotherapy of carboplatin combined with paclitaxel can provide complete and partial response rates of 8% to 33% and 50% to 85%, respectively [16]. Combination immunotherapy, especially immunochemotherapy, has shown better response rate in a variety of cancers, so Tirellizumab combined with carboplatin and paclitaxel has a strong application in oral cancer [7,8,16].