Serological Markers Associated With Response to Immune Checkpoint Blockade in Metastatic Gastrointestinal Tract Cancer.

ABSTRACT:

Importance

There are a limited number of predictive biomarkers for hyperprogressive disease (HPD), which is induced by immune checkpoint blockade (ICB) therapy.

Objective

To evaluate the association of biomarkers in serum with the response to ICB therapy in patients with metastatic gastrointestinal tract cancer.

Design, setting, and participants

Cohort study in which patients with metastatic gastrointestinal tract cancer treated with ICB were enrolled at the Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China, from August 1, 2015, to July 31, 2017, with the last follow-up date on January 1, 2018. Serum samples were collected at baseline and during the first visit to the clinic after starting treatment. Data analysis was conducted from January 16, 2018, to September 1, 2018.

Exposures

A total of 59 factors, including cytokines/chemokines, growth factors, and soluble checkpoint-related proteins in serum, were examined by multiplexed bead immunoassays.

Main outcomes and measures

Tree-based estimators were used to evaluate the importance of serum protein levels to ICB treatment response. Progression-free survival and overall survival analyses were conducted with the Kaplan-Meier method and log-rank test.

Results

In total, 56 patients were examined. All patients with HPD (5 [8.9%]) had significantly lower mean (SD) levels of serum monocyte chemoattractant protein 1 than patients without HPD at baseline (53.4 [17.3] pg/mL vs 106.4 [48.4] pg/mL; P?=?.02). All patients with HPD were also identified by lower leukemia inhibitory factor levels (<13.28 pg/mL) and higher cluster of differentiation 152 levels (?31.81 pg/mL). Among the remaining 51 patients, responders with esophageal squamous cell carcinoma (ESCC) or colorectal cancer (CRC) showed larger decreases in interleukin 1 receptor antagonist levels than nonresponders (ESCC: -55.02% [95% CI, -86.52% to -23.51%] vs 43.44% [95% CI, 11.93% to 74.96%]; P?Conclusions and relevanceIn this study, baseline serum levels of monocyte chemoattractant protein 1, leukemia inhibitory factor, and cluster of differentiation 152 were associated with hyperprogressive metastatic gastrointestinal cancer among patients receiving ICB. An early decrease in serum interleukin 1 receptor antagonist levels in patients with metastatic ESCC or CRC and an early increase in serum brain-derived neurotrophic factor levels in patients with metastatic GC were better able to identify who would respond to ICB compared with microsatellite stability status or programmed cell death ligand 1 expression.

SUBMITTER: Lu Z 

PROVIDER: S-EPMC6659353 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature