Efficacy and safety analysis of immune checkpoint inhibitor rechallenge in advanced esophageal squamous cell carcinoma: A retrospective study

New treatment strategies are needed for patients who relapse during or following first-line immune checkpoint inhibitor-based treatment for esophageal squamous cell carcinoma (ESCC). Second-line immune checkpoint inhibitors (ICI) rechallenge aims to reactivate the immune system's response to tumor cells and may improve the prognosis of patients who progressed during or after completing previous treatment. The purpose of this study is to explore the effectiveness and safety of second-line ICI rechallenge therapy in the treatment of advanced ESCC. We retrospectively reviewed the records of patients with advanced ESCC at the Department of Oncology of Jiangsu Cancer Hospital (January 2021 to June 2023) who had at least one measurable lesion at progression after first-line immunotherapy, received at least two cycles of second-line treatment, and who had subsequently undergone radiographic response assessment. The primary outcomes of interest were the progression-free survival (PFS)and overall survival (OS). Treatment-related adverse events were also recorded. In the ICI rechallenge and non-ICI rechallenge groups, the objective response rate (ORR) was 15.4% and 11.8%, the disease control rate (DCR) was 67.6% and 44.1% (<i>P</i> = .011). Compared with the non-ICI rechallenge group, median PFS2 in the ICI rechallenge group was significantly prolonged (5.63 <i>vs</i>. 3.03 months, hazard ratio [HR] = 0.45, 95% confidence interval [CI]: 0.28, 0.73; <i>P</i> = .001), while there was no statistically significant difference in median OS (12.33 <i>vs</i>. 7.10 months, HR: 0.80, 95% CI: 0.51, 1.27; <i>P</i> = .344). ICI rechallenge therapy and radiotherapy administered during second-line treatment were recognized as independent predictive factors influencing PFS2. These findings suggest that second-line ICI rechallenge is tolerable and could benefit a subset of patients with advanced ESCC.