Multicenter prospective trial of non-invasive predictors of response to paclitaxel plus ramucirumab in advanced gastric cancer

Paclitaxel plus ramucirumab (PTX + RAM) is a standard second-line treatment for advanced gastric cancer, but no validated biomarkers to predict response are know. The multicenter prospective IVY trial evaluated the predictive potential of exosomal microRNAs (exo-miRNAs) in 115 patients with advanced gastric cancer receiving PTX + RAM. Ten candidate exo-miRNAs were initially discovered, and a five-miRNA panel (miRNA 10a-5p, 25-5p, 125a-5p, 139-5p, and 450a-5p) was selected via stepwise elimination. This 5-exo-miRNA model achieved high accuracy in distinguishing controlled disease patients from progressive disease patients (AUC 0.84). When combined with body mass index, the composite model (EXEMPLAR) demonstrated enhanced predictive performance (AUC 0.87). High-risk patients exhibited significantly shorter progression-free survival (median 1.9 versus 4.2 months; p=0.019) and overall survival (median 1.1 versus 1.7 years; p<0.001) compared with low-risk patients. The authors conclude that the combined exosomal signature and BMI risk model provides a clinically applicable, non-invasive tool for personalized treatment selection.