S24.0.1. Integrating Anti-CTLA4 Salvage With Locoregional Therapy After Anti-PD-1 in Liver-Dominant Metastatic ESCC

Abstract

Esophageal Cancer: Management of Metastatic Cancer The 70-year-old man was diagnosed with squamous cell carcinoma of the mid-esophagus and underwent endoscopic submucosal dissection (ESD) in November 2022. Pathology demonstrated pT1b disease with negative margins but lymphovascular invasion (LVI) present. Given the adverse pathologic feature, he underwent additional lymph node dissection, which confirmed pN0 disease. He was followed with surveillance until September 2024, when he developed local recurrence accompanied by multiple liver metastases, establishing liver-dominant metastatic relapse. First-line systemic therapy was initiated from September to December 2024 with pembrolizumab in combination with paclitaxel, cisplatin, and 5-fluorouracil. Despite treatment, early imaging suggested progressive disease in the liver. He was enrolled into a second-line clinical trial of sacituzumab govitecan, a TROP2-directed antibody drug conjugate, from February to August 2025. Under sacituzumab govitecan, he achieved a radiographic partial response of hepatic lesions. However, subsequent imaging demonstrated liver metastasis progression, without evidence of widespread extrahepatic metastasis. The patient underwent radiofrequency ablation (RFA) of selected liver metastases for local control. Following LRT, subsequent systemic therapy using dual immune checkpoint inhibition with ipilimumab (1 mg/kg) plus nivolumab (3mg/kg). The patient achieved a good radiographic response (partial response, RECIST 1.1). The clinical benefit was achieved, but significant multisystem immune-related adverse events (irAEs) were noted. He developed immune-mediated colitis requiring corticosteroid-based immunosuppression, accompanied by rash. In addition, endocrine irAEs emerged, including hypothyroidism requiring thyroid hormone replacement and adrenal insufficiency, necessitating long-term hormone replacement and close monitoring. The proposed Expert Panel discussion will focus on questions relevant to contemporary ESCC management: (1) how to optimally sequence therapies after failure of PD-1-base therapy in advanced or metastatic ESCC, (2) how to incorporate liver-directed strategies for liver-dominant disease or oligoprogression; and (3) after a favorable response to ipilimumab plus nivolumab complicated by severe multisystem irAEs, what is the most evidence-aligned approach to continuation, de-escalation, or discontinuation with close surveillance.