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