Early Tumor Shrinkage and Clinical Outcomes for Esophageal Squamous Cell Carcinoma Patients Treated with Immune Checkpoint Inhibitors: Real-World Observational Study

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become a viable treatment method for unresectable or recurrent esophageal squamous cell carcinoma (ESCC). However, the relationships between early tumor shrinkage (ETS) and clinical outcomes for ESCC patients receiving ICIs remain unknown. This observational study investigated the associations between ETS and clinical outcomes for patients with unresectable or recurrent ESCC who received ICIs. METHODS: Early tumor shrinkage was defined as the percentage decreases at the first evaluation, and the ETS cutoff value was 20%. Using an unbiased database of 128 unresectable or recurrent ESCC patients who received ICI plus chemotherapy or ICI plus ICI, this study evaluated the relationships between ETS and clinical outcomes by multivariable Cox proportional hazards regression models to adjust for potential confounders, including the clinical and pathologic features. RESULTS: Among the patients, 52% had an ETS of 20% or more, and 48% had an ETS smaller than 20%. The ETS was not significantly associated with any of the clinical or pathologic features examined (all P > 0.09). However, ETS was significantly associated with longer progression-free survival (P < 0.01). Compared with the ETS-absent group, the multivariable-adjusted hazard ratio (HR) for the ETS-present group was 0.23 (95% confidence interval [Cl], 0.14-0.39; P < 0.01). Similarly, the same trend was observed for overall survival (multivariable-adjusted HR, 0.15; 95% CI, 0.07-0.31; P < 0.01). These prognostic associations of ETS were similarly observed in the ICI+chemotherapy and ICI+ICI groups (all P < 0.01). CONCLUSIONS: Early tumor shrinkage was associated with favorable clinical outcomes for ICI-treated patients with unresectable or recurrent ESCC, providing a platform for further investigations of predictive markers and treatment strategies.