Journal Article

Tislelizumab plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy for elderly patients with inoperable locally advanced esophageal squamous cell carcinoma: a multicenter, randomized, parallel-controlled, phase II clinical trial

Zhang, Ke, Xiao, Qin, Chen, Xi, Li, Zewei, Fan, Chengcheng, Zhang, Wencheng, Ge, Xiaolin, Liu, Xiao, Wang, Ping, Wang, Qifeng, Shen, Wenbin, Zhang, Tian, Dong, Jie, Cao, Jianzhong, Yan, Cihui, Pang, Qingsong, Zheng, Zhunhao

2025

Overview

Background The standard treatment for elderly patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is definitive chemoradiotherapy with S-1. However, the 3-year overall survival (OS) is limited to approximately 40%. Tislelizumab is the first- and second-line standard treatment for advanced ESCC with tolerable toxicity. In this study, we aimed to explore a new curative strategy for locally advanced unresectable ESCC in the elderly by combining tislelizumab with chemoradiotherapy. Methods This study is an open-label, multicenter, investigator-initiated phase II clinical trial in older patients with inoperable locally advanced ESCC evaluating tislelizumab plus concurrent chemoradiotherapy compared with concurrent chemoradiotherapy. The main inclusion criteria were pathological confirmation of locally advanced inoperable ESCC at clinical cT1N2-3M0 or cT2-4bN0-3M0 (stage II–IVA), age ≥ 70 years, absence of previous systemic anti-tumor therapy, and adequate organ function. A total of 136 patients will be recruited from approximately seven centers (in Tianjin, Chengdu, Taiyuan, Zhengzhou, Shijiazhuang, Changsha, Nanjing) over a period of 18 months and randomized in a 1:1 ratio to receive tislelizumab in combination with concurrent chemoradiotherapy (tislelizumab + S-1 + radiotherapy) or concurrent chemoradiotherapy (S-1 + radiotherapy). The efficacy and safety of the treatment will be evaluated during the therapy and follow-up period until disease progression, death, or the end of the trial. The primary study endpoint was investigator-assessed progression-free survival (PFS), and secondary study endpoints were OS, objective response rate (ORR), duration of remission (DOR), and safety. Fresh or archival tumor tissues and peripheral blood samples will be used in exploratory studies. Discussion This study is the first “programmed death-1 (PD-1) inhibitor combined with concurrent chemoradiotherapy” for elderly patients with inoperable locally advanced ESCC (NCT06061146). The synergistic efficacy of combined definitive concurrent chemoradiotherapy with tislelizumab is expected to result in survival benefits for elderly patients with inoperable locally advanced ESCC. Because S-1 plus concurrent radiotherapy is the standard treatment option for locally advanced ESCC in older patients, the combination of definitive concurrent chemoradiotherapy and tislelizumab has the potential to change the standard ESCC therapeutic strategy with comparable safety. Trial registration ClinicalTrials.gov NCT06061146.Registered 9/10/2023.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aged / Aged patients / Aged, 80 and over / Antibodies, Monoclonal, Humanized - administration & dosage / Antibodies, Monoclonal, Humanized - adverse effects / Antibodies, Monoclonal, Humanized - therapeutic use / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Apoptosis / Autoimmune diseases / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Cancer therapies / Care and treatment / Chemoradiotherapy / Chemoradiotherapy - methods / Chemotherapy / Clinical trials / Clinical Trials, Phase II as Topic / Concurrent chemoradiotherapy / Disease / Esophageal cancer / Esophageal carcinoma / Esophageal Neoplasms - drug therapy / Esophageal Neoplasms - mortality / Esophageal Neoplasms - pathology / Esophageal Neoplasms - therapy / Esophageal Squamous Cell Carcinoma - drug therapy / Esophageal Squamous Cell Carcinoma - mortality / Esophageal Squamous Cell Carcinoma - pathology / Esophageal Squamous Cell Carcinoma - therapy / Female / Health Promotion and Disease Prevention / Hospitals / Humans / Immunotherapy / Locally advanced esophageal squamous cell carcinoma / Male / Medical prognosis / Medicine/Public Health / Metastasis / Methods / Multicenter Studies as Topic / Older patients / Oncology / Patient outcomes / Patients / PD-1 protein / Peripheral blood / Radiation therapy / Radiotherapy / Randomized Controlled Trials as Topic / Remission / Squamous cell carcinoma / Study Protocol / Surgery / Surgical Oncology / Tislelizumab / Toxicity / Tumors