Relationship between immune-related adverse events and long-term survival in patients treated with immune checkpoint inhibitors for unresectable advanced or recurrent esophageal cancer

Summary Predictors of treatment outcomes for immune checkpoint inhibitors (ICIs) remain controversial. This study investigated the association between the occurrence of immune-related adverse events (irAEs) and treatment outcomes in patients with unresectable advanced or recurrent esophageal cancer (EC) receiving ICI combination regimens. This single-center retrospective study evaluated patients with unresectable or recurrent esophageal cancer treated with ICI combination regimens, including ICI + chemotherapy or ICI + ICI. Patients were categorized into irAE (+) and irAE (−) groups. Clinical outcomes, including progression-free survival (PFS), overall survival (OS), and complete response (CR)/partial response (PR) rate, were compared between the two groups. Survival curves were estimated using the Kaplan–Meier method and compared via log-rank tests, and independent prognostic factors were identified using multivariate Cox proportional hazards models. A total of 100 patients were included, consisting of 28 (28.0%) in the irAE (+) group and 72 (72.0%) in the irAE (−) group. The study cohort comprised 82 males and 18 females (median age: 70 years). Fifty-three patients had unresectable EC, whereas 47 had recurrent EC. Eighty-three patients received an ICI + chemotherapy regimen, and 17 received an ICI + ICI regimen. The irAE (+) group showed significantly better PFS and OS compared with the irAE (−) group (P 0.001 and P = 0.020, respectively). Significantly improved survival outcomes in the irAE (+) group were also observed in PFS of ICI + chemotherapy and in both PFS and OS of ICI + ICI. In multivariate analysis, performance status ≥2 and occurrence of irAE were identified as independently associated factors for shorter and longer PFS, respectively (P = 0.012 and 0.003). Although the irAE (+) group showed a numerically higher CR/PR rate than the irAE (−) group, no statistically significant difference was observed. IrAE occurrence was identified as an independent factor associated with improved PFS in patients with unresectable or recurrent EC who were treated with ICI combination regimens. They may serve as useful predictors for identifying patients likely to benefit from ICI treatment.