929P - Biomarker analyses of ramucirumab in patients with platinum refractory urothelial cancer from RANGE, a global, randomized, double-blind, phase III study

Abstract

BackgroundRANGE previously reported positive progression-free survival1 and a trend towards improved overall survival (OS)2 in ramucirumab (RAM) treated patients. Exploratory biomarker analysis of efficacy by programmed death-ligand 1 (PD-L1) expression revealed a hazard ratio (HR) for OS of 0.519, p=0.0048 in patients with a PD-L1 combined positive score (CPS)≥10 compared to HR of 0.999, p=0.9955 in patients with a PD-L1 CPS<10. We aim to understand prognostic and predictive factors related to survival outcomes in RANGE, and to identify patients who may benefit from RAM therapy using PD-L1 immunohistochemistry and gene expression analysis, defining molecular subtypes, and tumour microenvironment signatures. MethodsArchival tumour specimens that met assay stability requirements (238/530 ITT patients in RANGE) were analyzed with the 22C3 PD-L1 antibody with CPS based on tumour cell (TC) and immune cell (IC) staining. RNA expression analysis on archival tumour tissue (394/530 ITT patients) was done by GenomeDx (RNA microarray)3. PD-L1 groups, urothelial carcinoma molecular subtypes, and immune4 and stromal phenotypes5 were determined and analyzed for association with OS outcome. ResultsOverall, RAM had the greatest improvement in OS in patients with TC≥1, IC≥4 or CPS≥10 PD-L1 status. OS was also more improved in patients with basal subtypes, with considerable overlap noted between basal subtypes and TC≥1, IC≥4, or CPS ≥10 PD-L1 status. In the subgroup with both basal/basal claudin-low subtype and CPS≥10 PD-L1 status, median OS was 9.2 months with RAM and 6.0 months with placebo (stratified hazard ratio 0.47; 95% confidence interval: 0.27-0.84, p=0.01, n=79). ConclusionsOur analysis suggested significant improvement in OS in RAM treated patients with platinum refractory urothelial carcinoma, and with both basal subtype and positive PD-L1 status.