A Randomized Controlled, Non-inferior, Phase III Study of PD-1 Inhibitor Therapy Versus Radiotherapy in pCR Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma After Neoadjuvant Immunochemotherapy
In patients with locally advanced head and neck squamous cell carcinoma undergoing standard surgical treatment after neoadjuvant immunochemotherapy, can PD-1 inhibitor therapy be used instead of adjuvant radiotherapy for both primary and lymph node pathology? To provide further evidence-based medical evidence for the late precision treatment of HNSCC patients after neoadjuvant immunochemotherapy. Avoid the side effects caused by excessive radiotherapy, especially avoid the occurrence of second primary cancer, radiation osteonecrosis and other diseases. 1. Main study endpoint: A randomized controlled, non-inferiority, multicentre Phase III trial was conducted to investigate the difference in 5-year overall survival (OS) between experimental group (Group B) and control group (group A) in patients undergoing standard surgical treatment after neoadjuvant immunochemotherapy for locally advanced HNSCC, with both primary and lymph node pathology revealed by pCR. At the same time, adverse events and safety were evaluated according to NCI-CTCAE 5.0 criteria and RTOG later radiotherapy damage evaluation criteria. Safety indicators focused on late radiotherapy toxicity and the incidence of grade 3 and 4 adverse reactions in NCI-CTC AE 5.0 and RTOG. The differences in the incidence of grade 3 and 4 adverse events were compared between the experimental group and the control group. 2. Secondary study endpoint: The differences in 2-year disease-free survival (DFS), regional relapse-free survival (RRFS), distant metastasis free survival (DMFS), safety and adverse events were compared. Safety evaluation NCI-CTC AE 5.0 standard was used to evaluate the acute safety index of radiotherapy, and RTOG late-stage damage evaluation standard was used to evaluate the late-stage safety index of radiotherapy. 4\) Exploratory goals The influence of prognostic laboratory indicators, clinical risk factors were analyzed. To explore the factors that influence the efficacy of radiotherapy after pCR immunotherapy.
• In this study, patients with locally advanced head and neck squamous cell carcinoma (AJCC 8th) who underwent standard surgical treatment after neoadjuvant immunochemotherapy and showed pCR in both primary lesions and lymph node pathology were selected. Locally advanced squamous cell carcinoma of head and neck includes: i) T3, N0, M0; 2) T1-T3, N1-N2, M0; 3) T4a, N0-2, M0.
• No history of other malignant tumors
• Ages 18-65
• Normal baseline inspection:
‣ The absolute value of neutrophil granulocyte (ANC) ≥1.5x109/L in the last 14 days without the use of granulocyte colony stimulating factor;
⁃ Platelets ≥100×109/L without blood transfusion in the past 14 days;
⁃ Hemoglobin \> without blood transfusion or use of erythropoietin within the last 14 days; 9g/dL;
⁃ Total bilirubin ≤1.5× upper limit of normal value (ULN);
⁃ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN (ALT or AST ≤5×ULN in patients with liver metastasis);
⁃ Serum creatinine ≤1.5×ULN and creatinine clearance (calculated by Cockcroft-Gault formula) ≥60 ml/min;
⁃ Good coagulation function, defined as International Standardized ratio (INR) or prothrombin time (PT) ≤1.5 times ULN;
⁃ Normal thyroid function, defined as thyroid stimulating hormone (TSH) within the normal range. Subjects whose baseline TSH is outside the normal range can be enrolled if total T3 (or FT3) and FT4 are within the normal range;
⁃ The myocardial enzyme profile was within the normal range (if the researchers comprehensively judged that the simple laboratory abnormality was not clinically significant, it was also allowed to be included);
‣ For female subjects of childbearing age, a urine or serum pregnancy test should be tested negative within 3 days prior to receiving the first study drug administration (day 1 of Cycle 1). If the urine pregnancy test results cannot be confirmed negative, a blood pregnancy test is requested. Women of non-reproductive age were defined as at least one year after menopause or having undergone surgical sterilization or hysterectomy;
‣ If there is a risk of conception, all subjects (male or female) shall use contraception with an annual failure rate of less than 1% for the entire duration of treatment up to 120 days after the last study drug administration (or 180 days after the last chemotherapeutic drug administration).
• 5 Sign informed consent