Abstract
BACKGROUND: Immune checkpoint inhibitor (ICI) has reshaped the treatment landscape of esophageal squamous cell carcinoma (ESCC). But most patients end up with disease progression and/or therapeutic intolerance. The subsequent ICI rechallenge raises some discussions. METHODS: A retrospective study was conducted to assess the efficacy and safety of reintroduction of ICI in patients with advanced or metastatic ESCC after first-line ICI failure. Outcomes included median overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and safety. Subgroup analysis and prognostic analysis were also performed. RESULTS: A total of 1320 patients were screened and 138 were enrolled: 109 received second-line ICI-based therapies, and 29 received non-ICI therapies. As of data cutoff on November 30, 2024, patients with ICI rechallenge, compared with non-ICI rechallenge, achieved an improved second-line OS (10.4 vs. 5.8 months; HR = 0.53, 95% CI: 0.33-0.84; p = 0.006) and showed a favorable PFS trend (5.0 vs. 3.0 months; HR = 0.75, 95% CI: 0.48-1.17; p = 0.202). The 6-month PFS rate was 42.9% versus 22.3%, and the 12-month OS rate was 41.5% versus 23.2%, respectively. The ORR was 30.3% versus13.8% and the DCR was 79.8% versus 58.6%, respectively. ICI combined with chemoradiotherapy was the most popular option for subsequent ICI rechallenge, with an OS of 11.2 months. Treatment-related adverse events of grade ≥ 3 occurred in 47 (43.1%) and 11 (37.9%) patients in the two groups. CONCLUSION: Second-line ICI rechallenge provided OS benefits in advanced or metastatic ESCC, with manageable safety. Further prospective study is warranted.