Survival outcome of sandwich therapy with induction chemoimmunotherapy followed by concurrent chemoradiotherapy and sequential immune maintenance therapy in locally advanced unresectable esophageal squamous cell carcinoma (ESCC) patients: A multi-cen

4068 Background: PD-1 inhibitor, combined with chemotherapy, is recommended in first-line treatment for metastatic ESCC, but its role remains undefined in locally advanced ESCC. This trial aimed to investigate the survival outcome and safety of the ‘Sandwich Therapy’ consisting of induction chemoimmunotherapy followed by definitive chemoradiotherapy (dCRT) and sequential immune maintenance therapy. Methods: This is a multicenter, prospective study. Patients with histologically confirmed, clinical stage I–IVA and unresectable esophageal squamous cell carcinoma (ESCC) were included. Patients received 1-8 cycles of chemoimmunotherapy (intravenous paclitaxel (175 mg/m 2 ) plus platinum-based chemotherapy), then concurrent chemoradiotherapy followed by tislelizumab (200mg intravenously, every 3 weeks) until disease progression or the end of the study. The primary outcome was progression-free survival (PFS). The secondary outcomes included overall survival (OS) and the incidence of adverse events (AE). Results: Between August 2022 and Aug 2025, 77 patients were enrolled and all proceeded to the immune maintenance therapy phase. The median age was 61 years (IQR 55-69), and 78% had clinical stage III or IV disease. With median follow-up of 19 months (95CI), median PFS was 17.0 months (95% CI:12.0–36.0) , with 1-, 2- and 3-year PFS rate of 56.4%, 39.9% and 25.6%, respectively. The median OS was 45.0 months (95%CI:20.1-69.3), with 1-, 2- and 3-year OS rate of 74.9%, 63.2% and 50%, respectively. The objective response rate (ORR) was 55.8%, and the disease control rate was 92.2%. Grade ≥3 AE occurred in 27 (35.1%) patients during the treatment. The most common grade ≥3 AE was lymphopenia, which was reported in 22 (28.6%) patients. Conclusions: For locally advanced ESCC, induction chemoimmunotherapy followed by dCRT and subsequent maintenance of immunotherapy may improve PFS and OS with a manageable safety profile. Clinical trial information: NCT05515315 .