Efficacy and Safety of PD-1 Inhibitor Combined With Chemotherapy in Locally Advanced (III-IVB) Poorly Differentiated Head and Neck Squamous Cell Carcinoma: a Multi Cohort, Prospective Phase II Study
Patients with locally advanced (stage III to stage IVB) poorly differentiated head and neck squamous cell carcinoma (excluding nasopharyngeal carcinoma) who meet the inclusion criteria will have their blood samples collected, tumor tissue samples or patient paraffin tissue, and slides for comprehensive genomic sequencing and analysis. The study is divided into two groups. Arm1 group: Patients with stage IVB (T4bNxM0) poorly differentiated head and neck squamous cell carcinoma (excluding nasopharyngeal carcinoma) will receive PD-1 combined with platinum-based chemotherapy and albumin-bound paclitaxel (dose according to the drug instructions) for 2 to 3 cycles (determined by the researcher based on tumor shrinkage). If the imaging achieves complete response (CR) or partial response (PR), suitable patients will undergo surgical treatment. Patients who are not suitable for surgery or have stable disease (SD)/progressive disease (PD) will receive concurrent chemoradiotherapy or concurrent chemoradiotherapy combined with PD-1 treatment (up to a total of 17 cycles). Arm2 group: Patients with stage III and IVA (T3NxM0, T4aNxM0) poorly differentiated head and neck squamous cell carcinoma (excluding nasopharyngeal carcinoma) will receive PD-1 combined with platinum-based chemotherapy and albumin-bound paclitaxel (dose according to the drug instructions) for 2 cycles. Patients who undergo surgery within 2 weeks will receive PD-1 monotherapy maintenance treatment or low-dose radiotherapy followed by PD-1 monotherapy maintenance treatment based on pathological results. Patients who do not achieve pathological complete response (pCR) and have positive surgical margins or extracapsular extension will receive concurrent chemoradiotherapy followed by PD-1 maintenance treatment (up to a total of 17 cycles). Patients without high-risk factors will receive PD-1 maintenance treatment after radiotherapy (up to a total of 17 cycles). After completion of treatment, all patients will be followed up every 3 months for 1 year. Subsequently, patients will be followed up every 6 months for 3 years. Thereafter, patients will be followed up annually. Patient recurrence and survival data will be recorded.
• Patients with locally advanced (III-IVB) poorly differentiated head and neck tumors (hypopharyngeal cancer, laryngeal cancer, oropharyngeal cancer, nasal cavity and sinus cancer, excluding nasopharyngeal cancer) with a confirmed diagnosis by histology and/or cytology;
• Patients who can receive systemic treatment or PD-1/L1 monotherapy before treatment;
• Patients in arm2 must be evaluated as having resectable tumors before treatment;
• The investigator believes that the patient can safely receive PD-1 combined with platinum-based and albumin-bound paclitaxel treatment;
• Age ≥ 18 years;
• ECOG (Eastern Cooperative Oncology Group) 0-1；
• Measurable disease defined by RECIST v1.1;
• Adequate bone marrow reserve and organ function: absolute neutrophil count (ANC) ≥ 1,000/μL, platelets ≥ 75,000/μL, hemoglobin ≥ 8g/dL, no transfusion or erythropoietin (EPO) dependence (within 7 days of assessment);
• Renal function: serum creatinine ≤ 1.5X upper limit of normal (ULN) OR measured or calculated creatinine clearance ≥ 60mL/min, creatinine level \> 1.5X institutional ULN. (GFR can also be used instead of creatinine or CrCl). Creatinine clearance should be calculated according to institutional standards;
• Liver function: For subjects with total bilirubin levels \>1.5 ULN, serum total bilirubin ≤1.5X ULN or direct bilirubin ≤ULN; For patients with liver metastasis, aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤2.5X ULN or ≤5X ULN; Albumin \> 2.5 mg/dL;
• Coagulation function: International normalized ratio (INR) or prothrombin time (PT) ≤1.5X ULN, if subjects require anticoagulant therapy, PT or PTT (partial thromboplastin time) should be within the allowable range of anticoagulant use;
• Women should agree to use contraception during the study and for 6 months after the end of the study (such as intrauterine devices (IUDs), contraceptive pills, or condoms); Within 7 days before study enrollment, serum or urine pregnancy test should be negative, and patients must be non-lactating; Men should agree to use contraception during the study and for 6 months after the end of the study.