Circulating miRNAs as potentially predictive biomarkers for chemoimmunotherapy in advanced biliary tract cancer: a post-hoc analysis of the phase II T1219 study

Circulating microRNAs (miRNAs) have not been investigated as predictive biomarkers in patients with advanced biliary tract cancer (ABTC) who received chemoimmunotherapy. In the single-arm phase II T1219 trial, 46 patients with ABTC received first-line nivolumab, gemcitabine, and S-1 treatment. Plasma samples were prospectively collected at baseline and 6 weeks after treatment for miRNA profiling. Among the 167 miRNAs analyzed, the baseline levels of hsa-miR-16-5p, hsa-miR-93-5p, and hsa-miR-126-3p were significantly elevated in the responders. High hsa-miR-16-5p expression was correlated with longer progression-free survival (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.12-0.85, p = 0.025) and overall survival (HR = 0.34, 95% CI = 0.07-0.7, p = 0.01). Post-treatment miRNA changes (e.g., hsa-miR-129-5p and hsa-miR-1254) were observed but were not significantly associated with survival. This study identified a three-miRNA signature with potential predictive value for chemoimmunotherapy in ABTC. Trial registration: NCT04172402, date of registration 2019/11/18.