Neoadjuvant Immunochemotherapy for LAOSCC

Neoadjuvant therapy (NAT) is regarded as an effective way to reduce or downgrade the locally advanced or aggressive cancers, and to improve the chance of eradication of the locoregional lesions by radical surgery and/or radiotherapy. However, there are still debates on the clinical value of NAT for patients with locally advanced oral squamous cell carcinoma (LAOSCC). In a series of clinical trials on neoadjuvant therapy for LAOSCC have been carried out by our research group, the pathological efficacy of neoadjuvant immunochemotherapy is superior to neoadjuvant immunotarget therapy, neoadjuvant chemotarget therapy, or neoadjuvant chemotherapy. And in the neoadjuvant immunochemotherapy clinical trial (NCT04473716), the results of the safety and efficacy of neoadjuvant regimen showed that the neoadjuvant regimen of immunochemotherapy was well tolerated, with an MPR rate of 60% and 2-year OS of 90%, which were better than previously reported patients receiving standard treatment for LAOSCC. However, limited to single-arm clinical trial, the patients with LAOSCC benefit from neoadjuvant immunochemotherapy for survival, randomized controlled trials with larger sample size are needed. The aim of present trial is to evaluate the prognostic efficacy of 2-year survival rate in patients with LAOSCC receiving neoadjuvant immunochemotherapy with tiralizumab, albumin paclitaxel and cisplatin followed by radical surgery and adjuvant therapy compared with standard therapy.

The patients with LAOSCC would receive NAT with tiralizumab, albumin paclitaxel and cisplatin followed by radical surgery and adjuvant therapy (the experimental group) or radical surgery and adjuvant therapy (the control group). A total number of 134 patients will be recruited. Neoadjuvant immunochemotherapy: for the patients who are randomly assigned to the experimental group, the palpable edges of the primary lesion (both the longest and shortest axis) would be marked before NAT by at least four points, which is 0.5cm away; 260mg/m2 albuminpaclitaxel intravenously on day 1 and day 22, with 75mg/m2 of cisplatin at an hour interval and 200mg of tislelizumab at an hour interval will be performed. NAT will be given every 3 weeks for 2 cycles, unless there is disease progression, unacceptable toxic effects, or withdrawal of consent by the patients. Surgery will be performed within 2 weeks after completion of NAT. Surgery: Radical resection of the primary lesion and full neck dissection with proper reconstruction will be performed. The safety margins of the primary lesion are 1.0-1.5cm far away from the palpable margins of the lesion; for patients who received NAT, the safety margins are 1.0cm away from the marks that were placed before NAT, to ensure the same extent surgery in both groups. Post-operative adjuvant therapy: radiotherapy will be arranged 4 to 6 weeks after surgery. Routine external beam radiotherapy, will be performed, and the dose is 1.8-2Gy/day, 5 days/week for 6 weeks, and totally 54-60Gy, in the patient with high risk features, concurrent chemotherapy with cisplatin of 80mg/m2 will be used; in the experimental group, adjuvant maintaining therapy of 200mg of tislelizumab, every 3 weeks, for one year will be used. A complete medical history will be obtained and tumor assessment will be performed at baseline. Clinical tumor response will be assessed by clinical evaluation, imaging evaluation will be characterized according to the criteria of response evaluation criteria in solid tumors (version 1.1) before surgery. Post-operative pathological response will be assessed by post-operative pathological examination. Patients will be followed-up by every three months in the first 2 years, every six months in the next 3-5 years, and once a year thereafter until death or data censoring. Overall survival will be calculated from the date of randomization to the date of death; event free survival will be calculated from the date of randomization to local recurrence, regional recurrence, distant metastasis, disease progress, or death; disease free survival will be calculated from the date of randomization to tumor recurrence or distant metastasis or death from any cause.