Early Initiation of Adjuvant Nivolumab After Esophagectomy Is Associated With Immune-related Liver Injury

Adjuvant nivolumab after esophagectomy is increasingly being adopted for patients with esophageal cancer. However, its safety and efficacy following neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) remain unclear. At our institution, we observed a high incidence of immunerelated liver injury (irLI). In this study, we evaluated the short-term outcomes of adjuvant nivolumab therapy and investigated the risk factors associated with irLI development.

This single-center study included 34 patients with thoracic esophageal squamous cell carcinoma who received neoadjuvant DCF, underwent esophagectomy, and were administered adjuvant nivolumab between 2022 and 2024. Patient demographics, details of adverse events, including irLI, and short-term survival data were retrospectively collected from medical records. Clinicopathological features associated with irLI were evaluated using univariate and multivariate analyses.

Adverse events related to adjuvant nivolumab occurred in 22 of 34 patients (64.7%), and irLI developed in 14 of 34 patients (41.2%); all irLI cases were Common Terminology Criteria for Adverse Events Grade ≥3. The median interval from surgery to nivolumab initiation was 28 days in the patients who developed irLI. IrLI occurred in 13 of 22 patients (59.1%) who initiated nivolumab <8 weeks postoperatively versus 1 of 12 patients (8.3%) who initiated at ≥8 weeks after surgery. In multivariate analysis, early initiation of nivolumab (<8 weeks) was the only independent predictor of irLI.

Early initiation of adjuvant nivolumab therapy after neoadjuvant DCF and esophagectomy is associated with a higher incidence of irLI.