1404P - Predictive role of circulating cytokines in esophageal squamous cell carcinoma receiving chemoradiotherapy combined with anti-PD1 inhibitor: Pooled analyses of two phase II clinical trials

Background

Combination of anti-PD1 inhibitor with chemoradiotherapy (CRT) has been shown to improve the survival of patients with locally advanced esophageal squamous cell carcinoma (ESCC). This study specifically aims to identify circulating cytokines as biomarkers for predicting treatment response, survival, and immune-related toxicities.

Methods

Patients with locally advanced ESCC from two phase II clinical trials (EC-CRT-001 and NEOCRTEC1901) were pooled for analysis. All patients received CRT in combination with toripalimab, an anti-PD1 inhibitor. We longitudinally profiled 19 cytokines in the plasma before (pre), during, and after (post) CRT. The associations between cytokine levels and treatment response or immune-related toxicity were examined using the Wilcoxon test. Their correlations with overall survival (OS) and progression-free survival (PFS) were assessed through univariate and multivariate Cox analyses.

Results

A total of 81 patients were included, and 243 plasma samples were analyzed. Multivariate analyses indicated that pre-treatment levels of IL-8 and post-treatment levels of Granzyme B were independent prognostic markers for OS (p<0.05). Post-CRT levels of IL-10 were identified as independent prognostic markers for PFS (p<0.05). Subgroup analyses revealed correlations between pre- and during-CRT levels of IL-8, and post-CRT levels of IL-13 and IL-10 with a complete clinical response in the EC-CRT-001 group. Additionally, pre-CRT IL-8 and post-CRT CCL5 levels were associated with immune-related toxicities.

Conclusions

Circulating cytokines, particularly IL-8, serve as significant biomarkers for predicting response, survival, and immune-related toxicities in locally advanced ESCC patients undergoing combined chemoradiotherapy and toripalimab treatment.

Clinical trial identification

NCT04005170; NCT04006041.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.