Neoadjuvant toripalimab combined with gemcitabine and cisplatin in resectable locally advanced head and neck squamous cell carcinoma (NeoTGP01): An open label, single-arm, phase Ib clinical trial

• DOI: 10.1186/s13046-022-02510-2
• Publication Date: 2022-10-12T14:04:12Z
• Authors: Xiaotao Huang; Qiaodan Liu; Guihua Zhong; Yingpeng Peng; Ye Liu; Lizhong Liang; Haiyu Hong; Weineng Feng; Shuang Yang; Yaqin Zhang; Shiping Xian; Zhanyu Li; Yuling Zhou; Zhaoyuan Zhang; Wen Jiang; Jun Liang; Zhi-gang Liu
• Keywords: Neoadjuvant treatment; Medical Sciences; Bioinformatics; Programmed Cell Death 1 Receptor; 610; Antibodies, Monoclonal, Humanized; Deoxycytidine; Antibodies; Biomedical Informatics; 03 medical and health sciences; 0302 clinical medicine; Death Domain; Monoclonal; Receptors; Antineoplastic Combined Chemotherapy Protocols; Medical Specialties; Medicine and Health Sciences; Humans; Humanized; Immune Checkpoint Inhibitors; RC254-282; Squamous Cell Carcinoma of Head and Neck; Research; Pathological response rate; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Head and neck squamous cell carcinoma; Receptors, Death Domain; Gemcitabine; Neoadjuvant Therapy; 3. Good health; Oncology; Head and Neck Neoplasms; Immunotherapy; Cisplatin

Abstract Background Neoadjuvant programmed death receptor-1 (PD-1) inhibitors have drawn increasing attention in locally advanced head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the safety and efficacy of gemcitabine and cisplatin (GP), combined with a PD-1 inhibitor, in patients with locally advanced HNSCC.

Materials and methods A total of 23 eligible patients were administered two cycles of toripalimab and GP followed by surgical resection. The primary endpoints were safety, treatment-related adverse events (TRAEs), and non-operation delay rates. The secondary endpoints consisted of pathological complete response (pCR) rate, major pathological response (MPR) rate, objective response rate (ORR), and R0 resection rate.

Results The incidence of TRAEs from grades 1 to 4 was 43.5%, 34.8%, 13.0%, and 8.7%, respectively. Grade 3/4 TRAEs included neutropenia, fatigue, hyperglycemia, nausea and vomiting, decreased appetite, rash, and diarrhea. No treatment-related surgical delay was observed. The radiographic response rates were 5.0% (CR), 40.0% (PR), and 55.0% (SD). The ORR reached 45.0%. Eighteen patients underwent successful surgical resection. The R0 resection rate was 100%. The pathological response rates were 16.7% (pCR), 27.8% (MPR, two of five near-pCR), 16.7% (PPR), and 38.8% (NPR). CD4, CD8, CD20, and CD38 expression in the tumors significantly increased after neoadjuvant chemotherapy. The increase in CD20 levels after neoadjuvant treatment in patients with pCR/MPR was significantly higher than in patients with PPR/NPR.

Conclusion Triweekly neoadjuvant toripalimab-GP is feasible and achieves promising pCR and MPR rates in patients with resectable locally advanced HNSCC.

Trial registration Chinese clinical trial registry, ChiCTR2100043743, Registered 27 Febrary 2021- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=120570