860P - Pembrolizumab in combination with low-dose cisplatin/5-fluorouracil for neoadjuvant chemoimmunotherapy of locally advanced head and neck squamous cell carcinoma: A single-arm clinical trial

Background

Head and Neck Squamous Cell Carcinoma (HNSCC) presents a significant global health challenge. Neoadjuvant chemoimmunotherapy (NAC) has become vital strategies for treating relapsed or metastatic HNSCC, limited by the toxicity associated with conventional dosages. However, effective strategies for locally advanced HNSCC (LA-HNSCC) remain underdeveloped. Combining PD-1/PD-L1 inhibitors with other treatment modalities shows promise. Our study evaluates the efficacy and safety of pembrolizumab combined with low-dose cisplatin/5-fluorouracil (PLPF) for treating patients (Pts) with LA-HNSCC.

Methods

In this single-center, open-label, single-arm study, Pts aged ≥18 with untreated LA-HNSCC per AJCC 8th edition were eligible for 6 cycles of preoperative PLPF therapy, requiring a measurable tumor, no distant metastases, and adequate organ function. The primary endpoint was complete response rate, with secondary endpoints including overall response rate (ORR) and pathological complete response (pCR), assessed by RECIST 1.1. Adverse events (AE) were graded according to CTCAE v6.0. The efficacy of PLPF therapy was further evaluated through single-cell sequencing (SCS).

Results

A total of 24 Pts with LA-HNSCC were enrolled from April 2021 to May 2023. The median age was 62.5 years. After PLPF therapy, 18 Pts underwent primary tumor surgery, achieving a 61.11% pCR. The ORR was 100%, with complete and partial responses in 71.43% and 28.57% of Pts, respectively. All Pts showed imaging and clinical downstaging, with a tracheotomy rate of 0% and an organ preservation rate of 100%. The median follow-up time was 25.0 months (range 8.4-36.2), as of the cut-off date of April 31, 2024. Grade 3 or higher AE were low, primarily hematological. SCS result revealed that enhancing the anti-tumor capacity by changing the percentage of CD8⁺ Tex and CD8⁺ Tem.

Conclusions

PLPF therapy demonstrates efficacy in treating LA-HNSCC, showing promising clinical outcomes. Compared to the conventional NAC, this regimen significantly enhances safety. However, further validation through large-scale clinical trials is imperative.

Clinical trial identification

ChiCTR2200065597, Registered 9 November 2022.

Editorial acknowledgement

During the preparation of this work the authors used ChatGPT in order to improve language expression. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication. The above guidance only refers to the writing process.

Legal entity responsible for the study

Zhejiang Provincial People's Hospital medical center.

Funding

Scientific Research Fund of the National Health Commission -- Zhejiang Provincial Health Major science and technology Plan project, WKJ-ZJ-2415 the Key Research and Development Program of Zhejiang Province (2024C03166) Zhejiang Provincial Natural Science Foundation [grant number LY21H160049].

Disclosure

All authors have declared no conflicts of interest.