PD-1 Inhibitor Therapy Versus Radiotherapy in MPR Patients With Locally Advanced HNSCC After Neoadjuvant Immunochemotherapy (HNC-SYSU-006)

Summary

Head and neck malignant tumors rank as the sixth most common type of malignancy worldwide, with approximately 90% being squamous cell carcinoma (Head and Neck Squamous Cell Carcinoma, HNSCC). Globally, there are about 650,000 new cases of HNSCC annually, with China contributing approximately 350,000 new cases each year. At initial diagnosis, 60% of patients already present with locally advanced HNSCC, necessitating comprehensive treatment strategies.

In the first half of the 20th century, radiotherapy was the primary treatment for HNSCC. However, due to its relatively low local control rate (70%), high rate of distant metastasis (20%), and low 5-year overall survival (OS) rate (40%), coupled with significant early and late adverse effects, radiotherapy often brought severe challenges to patients. For instance, 95% of patients developed radiation-induced oral mucositis, nearly all experienced xerostomia, taste disorders, radiation-induced dental caries, restricted mouth opening, swallowing difficulties, aspiration, and other functional impairments. Some patients even suffered severe complications, with 6% developing radiation-induced osteonecrosis of the jaw, and 0.1% experiencing secondary cancers such as radiation-induced sarcoma or squamous cell carcinoma in the head and neck region. Other complications, such as radiation-induced encephalopathy, also posed significant threats to patients' safety and quality of life. As surgical techniques improved towards the end of the 20th century, surgery gradually replaced radiotherapy as the dominant treatment for HNSCC.

Over the past four decades, despite the use of comprehensive treatments based on surgery supplemented by radiotherapy, chemotherapy, and targeted therapy, the 5-year survival rate for locally advanced HNSCC has not significantly improved, remaining around 50%. Recently, with the advent of immunotherapy centered on PD-1 inhibitors, treatment outcomes for HNSCC patients have improved markedly, and the therapeutic landscape is undergoing significant transformation. Concurrently, many studies have focused on neoadjuvant immunotherapy prior to surgery. In locally advanced lung cancer, neoadjuvant chemoimmunotherapy has been proven safe and effective through phase III clinical trials. Similarly, studies on head and neck tumors have shown that neoadjuvant immunotherapy-whether PD-1 monotherapy or in combination with chemotherapy-demonstrates favorable safety and efficacy. However, for patients who respond well to immunochemotherapy and achieve pathological downstaging, how to evaluate the relationship between therapeutic efficacy, staging, and prognosis, as well as how to plan subsequent treatments, remains unclear in existing guidelines. For some patients with locally advanced HNSCC who achieve major pathological response (MPR) or pathological complete response (pCR) after neoadjuvant immunochemotherapy and undergo extensive primary tumor resection and thorough neck lymph node dissection, there is no research to clarify whether postoperative adjuvant radiotherapy based on pretreatment TNM staging is still necessary.

Some studies suggest that for patients with pN1 stage, adjuvant radiotherapy after thorough neck lymph node dissection does not significantly impact local control or long-term survival. Literature indicates that the recurrence rate of cervical lymph nodes in N1-stage head and neck squamous cell carcinoma is approximately 8%, meaning that about 92% of N1-stage patients who receive postoperative radiotherapy to the cervical lymphatic drainage area might be overtreated. For patients who achieve pCR after neoadjuvant immunochemotherapy, continuing radiotherapy in the original region after high-quality surgery further increases the likelihood of overtreatment. For locally advanced HNSCC patients who achieve pCR or MPR in the primary tumor and lymph nodes, whether routine radiotherapy should be administered following high-quality surgical resection and lymph node dissection remains controversial in the academic community.

This leads to our clinical question: In patients with locally advanced HNSCC who achieve MPR in both the primary tumor and lymph nodes after neoadjuvant immunochemotherapy and undergo standard surgical treatment, can maintenance therapy with PD-1 inhibitors replace adjuvant radiotherapy?

This study aims to enroll patients who have undergone neoadjuvant immunochemotherapy followed by standard surgical treatment and achieved MPR in both the primary tumor and lymph nodes. Patients will be divided into an experimental group and a control group. The experimental group will receive maintenance therapy with PD-1 inhibitors, while the control group will follow guideline-recommended adjuvant treatments (radiotherapy or concurrent chemoradiotherapy based on platinum compounds) according to tumor classification and staging before neoadjuvant immunochemotherapy. Outcomes such as 2-year

Conditions

• HNSCC
• PD-1
• Radiotherapy

Interventions

DRUG

PD-1inhibitor

The PD-1 monoclonal antibody was the same as the neoadjuvant therapy before surgery, and the postoperative level was maintained at Q3\*6.

RADIATION

radiotherapy

According to the guidelines, concurrent chemoradiotherapy is required, and carboplatin (50mg/m2) plus concurrent radiotherapy or cisplatin (30mg/m2) plus concurrent radiotherapy is optional.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-08-01

Primary Completion

2027-12-01

Completion

2031-12-31

Countries

• China

Study Locations