A pragmatic phase II trial evaluating treatment strategies using immune checkpoint inhibitors for metastatic esophageal cancer patients with severe dysphagia.

Introduction: The addition of immune checkpoint inhibitors (ICIs) to chemotherapy has significantly improved the prognosis of patients with metastatic esophageal cancer. Although fluorouracil and cisplatin (FP) combined with an ICI is considered one of the most effective first-line treatments, patients with severe dysphagia have not been adequately evaluated. Radiotherapy (RT) and chemoradiotherapy (CRT), however, have been established as effective treatment options for dysphagia, based on the results of a phase III clinical trial conducted before the approval of ICIs for esophageal cancer. This study aims to evaluate the efficacy and safety of FP plus ICI and FP plus ICI following RT/CRT in patients with stage IVB esophageal cancer and severe dysphagia. Methods: This is a randomized, non-comparative, pragmatic phase II trial enrolling untreated patients with metastatic esophageal or esophagogastric squamous cell carcinoma and severe dysphagia. Patients are randomized to receive either FP plus ICI (arm A) or FP plus ICI following RT/CRT (arm B) in accordance with clinical practice. The primary endpoint is dysphagia relief rate at 9 weeks from the initiation of treatment. This trial has been ongoing since December 2024.