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

Abstract Background The standard treatment for elderly patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is definitive chemoradiotherapy based on S-1. However, 3-year overall survival (OS)is limited about 40%. Tislelizumab has been the first-line and second-line standard treatment for advanced ESCC with tolerable toxicity. In the study we aimed to explore a new curative strategy for locally advanced unresectable elderly ESCC by combining tislelizumab with chemoradiotherapy. Methods The 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 to concurrent chemoradiotherapy. The main inclusion criteria are pathological confirmation of locally advanced inoperable ESCC at clinical cT1N2-3M0 or cT2-4bN0-3M0(stage II–IVA), aged ≥ 70 years, without any previous systemic anti-tumor therapy, and adequate organ function. A total of 136 patients will be recruited from approximately 6 centers over a period of 1 year 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 treatment will be evaluated during the therapy and follow-up period until disease progression or death or the end of the trial. The primary study endpoint is investigator-assessed progression free survival (PFS), and the secondary study endpoints are OS, objective response rate (ORR), duration of remission (DOR), and safety. Fresh or archival tumor tissues and peripheral blood samples will be used in the exploratory studies. Discussion The synergistic efficacies of combined definitive concurrent chemoradiotherapy with tislelizumab are expected to result in survival benefit for elderly patients with inoperable locally advanced ESCC. As S-1 plus concurrent radiotherapy is the standard treatment option for locally advanced ESCC 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