Survival Results of Chemo-immunotherapy Sequential with Radiotherapy in Patients with Advanced or Metastatic Esophageal Squamous Cell Carcinoma

Background Chemotherapy plus immunotherapy improves overall survival (OS) for patients with advanced esophageal cancer. However, survival for this population remains inadequate, underscoring the need for more effective and less toxic treatment combinations to further extend patient survival. Objectives To evaluate the efficacy and safety with induction chemo-immunotherapy followed by sequential esophageal tumor irradiation in patients with advanced stage esophageal squamous cell carcinoma. Design: This is a single-arm, three-center, open-label study involving treatment-naïve patients with radiologically and histologically confirmed advanced or metastatic squamous-cell esophageal carcinoma. Methods Enrolled patients were treated with induction chemo-immunotherapy, residual esophageal tumor irradiation and immunotherapy consolidation. In the induction phase, participants received four cycles of the TP regimen, consisting of docetaxel (75 mg/m² IV on day 1) and cisplatin (75 mg/m² IV on day 1), combined with the PD-1 inhibitor sintilimab (200 mg IV on day 1) every 21 days. Patients who completed four cycles of chemo-immunotherapy with stable disease (SD) or partial response (PR) subsequently received 50 Gy of radiation in 25 fractions for residual tumors. Maintenance sintilimab therapy was administered every 21 days for up to 31 cycles or until disease progression or intolerable toxicity occurred. Results A total of 51 patients with histologically confirmed squamous-cell carcinoma were enrolled, and were evaluable for toxicity for they had had at least one dose of chemo-immunotherapy. The complete response (CR) rate was 5.9% (3/51), the partial response (PR) rate was 51.0% (26/51), and the disease control rate (DCR) was 90.2% (46/51) after chemo-immunotherapy. The median depth of response (DpR) was 35.0% for chemo-immunotherapy and was 51.0% after additional radiotherapy. The progression-free survival (PFS) was 16.4 months and the overall survival (OS) 29.25 months. The most common grade 3 or higher adverse event was neutropenia, occurring in 11.8% (6/51) patients. This study is registered with ClinicalTrials.gov (identifier NCT06138028) and is currently ongoing. The preliminary results of this study were reported and published on 2025 ASCO GI (DOI:10.1200/JCO.2025.43.4suppl.437). Conclusions Chemo-immunotherapy followed by radiotherapy for esophageal residual tumors and subsequent maintenance sintilimab, demonstrated high response rates, prolonged PFS and OS as a first-line treatment for patients with advanced or metastatic esophageal squamous-cell carcinoma. Patients with disease progression during the induction phase had a short PFS and OS, indicating this subgroup requires further study in the future.