3094 - Tislelizumab plus Chemotherapy Sequential Neoadjuvant Therapy for Non-cCR Patients after Neoadjuvant Chemoradiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma (ETNT): An Exploratory Stu

L. Peng¹, Q. Wang², W. He¹, Y. Han¹, T. Li³, and J. Lang⁴; ¹Department of Thoracic Surgery, Sichuan Cancer Hospital& Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China, ²Department of Radiation Oncology, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, China, ³Department of Radiation Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China, ⁴Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center; Cancer Hospital affiliate to University of Electronic Science and Technology of China, Chengdu, China

Purpose/Objective(s): Esophageal squamous cell carcinoma (ESCC) remains a challenging malignancy with a poor prognosis and limited treatment options worldwide. Despite the current standard treatment of neoadjuvant chemoradiotherapy plus surgery for resectable locally advanced ESCC, high rates of recurrence and metastasis continue to contribute to treatment failure. Enhancing the pathological complete response (pCR) rate could significantly improve the survival outcomes for patients with resectable locally advanced ESCC following neoadjuvant therapy. Materials/

Methods: Eligible patients for inclusion were aged 18-75 years with untreated, resectable stage III-IVA esophageal squamous cell carcinoma (ESCC), and had adequate organ and bone marrow function. The treatment regimen consisted of neoadjuvant chemoradiotherapy (paclitaxel 135 mg/m2 on day 1 + carboplatin AUC = 3–5 on day 1, every three weeks for two cycles) combined with simultaneous radiotherapy (40 Gy/4 W/20F). After completion of chemoradiotherapy, tumor regression was evaluated according to MDT criteria. Non-complete clinical response patients received tislelizumab (200 mg intravenously every three weeks for two cycles), followed by surgery after a period of four to six weeks. Primary outcomes included pathological complete response rate and incidence of adverse events, which will be analyzed within months. Secondary endpoints encompassed major pathological response rate, objective response rate, R0 resection rate, event-free survival, and overall survival. All enrolled patients were included in the activity and safety analyses. The trial is registered with ClinicalTrials.gov under NCT05189730.
Results: As of October 2023, a total of 63 patients were enrolled in the study, of whom 53 were available for analysis, but 4 patients were awaiting surgery, and another 49 patients underwent radical resection, with a resection rate of 100%. The median age of the patients was 66 years, and all patients had stage III-IVA disease. All patients completed the planned chemoradiotherapy, and 23 of 49 (46.9%) patients achieved pCR. Patients with CCR,9/16(56.2%)achieved a pCR. Among the patients who received chemotherapy with tirelizumab after chemoradiotherapy, 14/33 (42.4%)patients achieved a pCR. In the whole group, the objective response rate after chemoradiotherapy was 44(89.7%), and 30 (61.2%) patients achieved a major pathological response. For patients with non pCR, 19 (38.7%) patients continued to use tirelizumab. There were no deaths or anastomotic leakage within 30 days, and the most common adverse events were leukopenia, hypothyroidism, and lymphopenia. Survival analysis is immature, and patients are still being followed up.
Conclusion: This study explored the safety and efficacy of tislelizumab plus chemotherapy sequential neo-chemoradiotherapy therapy for ESCC patients and provided a total neoadjuvant therapy model that can patients benefit with locally advanced ESCC without CCR.