Head and neck squamous cell carcinoma (HNSCC) refers to a series of tumors that occur in the head and neck region, including the oral cavity, pharynx, larynx, nasal cavity, paranasal sinuses, thyroid gland, and salivary glands. Malignant tumors of the head and neck account for approximately 19.9% to 30.2% of all tumors in the body, ranking sixth in incidence among all malignant tumors, with over 90% being squamous cell carcinoma in terms of pathological type. The treatment of head and neck squamous cell carcinoma is primarily surgical. Early-stage cases can achieve a cure through simple surgical resection or radiotherapy. For locally advanced and late-stage cases, a combination of surgery with radiotherapy or chemotherapy can yield satisfactory therapeutic effects. However, most patients with head and neck tumors present at a locally advanced (Stage III to IVB) or late stage, possibly having lost the opportunity for surgery and can only opt for a comprehensive treatment mainly based on radiochemotherapy. Current data show that with standard treatment, the 5-year survival rates for patients with early-stage, locally advanced, and metastatic head and neck squamous cell carcinoma are 80%, 50%, and 25%, respectively. Fifty to sixty percent of newly diagnosed subjects cannot be cured and experience recurrence or metastasis within 3 years. For patients with recurrent or metastatic disease after first-line treatment failure, the median survival time with chemotherapy is only 6 to 9 months, with a 1-year survival rate of 5% to 33% and a 5-year survival rate of merely 3.6%. Laryngeal cancer and hypopharyngeal cancer hold unique significance among head and neck tumors because they not only threaten patients' lives but can also significantly affect their quality of life, particularly the preservation of laryngeal function. Laryngeal function includes voice production, swallowing, and breathing, and the loss of these functions can lead to a severe decline in quality of life. Traditionally, surgical resection has been the main treatment for these cancers, but total laryngectomy can result in permanent voice loss and significant psychological and social impacts. Therefore, how to effectively control the tumor while preserving laryngeal function has become an important goal of treatment.
PD-L1 is a key negative regulator of self-reactive T cells and plays a role in maintaining peripheral immune tolerance and suppressing autoimmunity in various ways, leading to T cell exhaustion and dysfunction, and allowing tumor cells to evade immune surveillance. PD-1/PD-L1 monoclonal antibodies restore the function of tumor-specific T cells by blocking the binding of PD-1 to PD-L1, thereby enhancing antitumor immunity and are now used to treat a variety of tumors. The efficacy of PD-1 inhibitors as neoadjuvant therapy in head and neck squamous cell carcinoma is not yet clear. However, given the good therapeutic effects of immunotherapy in head and neck squamous cell carcinoma, induction therapy with PD-1 inhibitors is considered to have promising clinical application prospects.
In summary, we hypothesize that compared with the traditional TPF (docetaxel, cisplatin, and fluorouracil) neoadjuvant chemotherapy regimen, a PD-1 inhibitor combined with chemotherapy regimen may be safer and more effective and easier to apply in clinical practice. At present, there are no reports of studies on the use of PD-1 inhibitors combined with chemotherapy regimens for locally advanced, resectable head and neck squamous cell carcinoma patients, either domestically or internationally. We plan to investigate the efficacy and safety of neoadjuvant treatment with PD-1 inhibitors combined with chemotherapy for resectable head and neck squamous cell carcinoma patients in China, to provide a basis for future neoadjuvant treatment regimens.
Patients with locally advanced laryngeal and hypopharyngeal squamous cell carcinoma who have been definitively diagnosed by histology and/or cytology, and whose TN staging meets: T1-4a, N0-3.
No prior treatment received.
Cisplatin-tolerant.
Age ≥18 years.
T stage is T4b.
Presence of distant metastasis.
Received live vaccines within 30 days prior to enrollment.
Diagnosed with an immunodeficiency or received systemic corticosteroid treatment or any other form of immunosuppressive therapy within 7 days prior to enrollment.
Parallel
Pembrolizumab
DrugPembrolizumab 200mg, IV, 3 cycles
Cisplatin
Drugcisplatin 75mg/m2, IV, 3 cycles
Nab-paclitaxel
DrugNab-paclitaxel 260mg, IV, 3 cycles
2-year progression-free survival rate (2y-PFS rate)
To evaluate the 2y-PFS rate of neoadjuvant PD-1 inhibitors combined with chemotherapy in 3 arms; PFS was defined as the time from patient enrollment to the occurrence of the following events (local progression/recurrence or distant metastasis (including neoadjuvant stage) assessed by imaging or biopsy, death from any cause)
Pathological complete response rate (pCR rate)
To evaluate the pCR rate of neoadjuvant PD-1 inhibitors combined with chemotherapy in 3 arms; pCR was defined as the absence of residual invasive squamous cell carcinoma cells in the resected primary tumor specimen and lymph nodes
Objective response rate (ORR)
To evaluate the ORR of neoadjuvant therapy with PD-1 inhibitors plus chemotherapy in 3 Arms; ORR is defined as The proportion of patients whose tumor volume shrinks to a pre-specified value and can be maintained for a certain period of time. It includes the proportion of patients with complete remission (CR) and partial remission (PR) to the total number of evaluable cases.
2-year overall survival rate (2y-OS rate)
To evaluate the 2y-OS rate of neoadjuvant PD-1 inhibitors plus chemotherapy in 3 Arms; OS was defined as the time from randomization until death from any cause.
Progression-Free Survival(PFS)
To evaluate the PFS of neoadjuvant PD-1 inhibitors plus chemotherapy in 3 arms in the overall population; PFS is defined as the length of time during and after treatment that a patient lives with a disease that does not get worse.
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