Efficacy and Safety of Immune Checkpoint Inhibitor Rechallenge in the Treatment of Esophageal Squamous Cell Cancer

<b>Background:</b> Rechallenge with immune checkpoint inhibitors (ICI) shows promise in various cancers, but data in esophageal squamous cell carcinoma (ESCC) is limited. This study aimed to evaluate the efficiency and safety of ICI rechallenge in ESCC. <b>Materials and Methods:</b> This multicenter study analyzed ESCC patients rechallenged with ICI from January 2020 to March 2023 across two medical institutions. Patients were divided into rechallenge (R) and non-rechallenge (NR) groups. Key outcomes studied were progression-free survival (PFS), overall survival (OS), and safety. <b>Results:</b> Among 329 included ESCC patients, 211 were in the R group and 118 in the NR group, with a median follow-up of 17.1 months. The R group exhibited significantly prolonged median PFS (4.7 vs. 3.2 months; p <.001) and OS (9.3 vs. 6.2 months; p <.001) compared to the NR group. Notably, for patients who initially received radiotherapy, the R group showed significantly longer mPFS (5.1 vs. 3.2 months; p <.001) and mOS (10.4 vs. 5.9 months; p <.001). Incidences of all-grade (64.5% vs. 66.1%; p = .764) and grade ≥3 adverse events (17.5% vs. 18.6%; p = .802) did not significantly differ between groups. <b>Conclusion:</b> ICI rechallenge demonstrates efficacy and manageable safety in ESCC, particularly post-radiotherapy.