Predictive biomarkers for survival benefit with ramucirumab in urothelial cancer in the RANGE trial

Nat Commun. 2022 Apr 6;13(1):1878. doi: 10.1038/s41467-022-29441-y.


The RANGE study (NCT02426125) evaluated ramucirumab (an anti-VEGFR2 monoclonal antibody) in patients with platinum-refractory advanced urothelial carcinoma (UC). Here, we use programmed cell death-ligand 1 (PD-L1) immunohistochemistry (IHC) and transcriptome analysis to evaluate the association of immune and angiogenesis pathways, and molecular subtypes, with overall survival (OS) in UC. Higher PD-L1 IHC and immune pathway scores, but not angiogenesis scores, are associated with greater ramucirumab OS benefit. Additionally, Basal subtypes, which have higher PD-L1 IHC and immune/angiogenesis pathway scores, show greater ramucirumab OS benefit compared to Luminal subtypes, which have relatively lower scores. Multivariable analysis suggests patients from East Asia as having lower immune/angiogenesis signature scores, which correlates with decreased ramucirumab OS benefit. Our data highlight the utility of multiple biomarkers including PD-L1, molecular subtype, and immune phenotype in identifying patients with UC who might derive the greatest benefit from treatment with ramucirumab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen / analysis
  • Biomarkers
  • Biomarkers, Tumor
  • Carcinoma, Transitional Cell* / pathology
  • Humans
  • Urinary Bladder Neoplasms* / drug therapy
  • Urinary Bladder Neoplasms* / pathology


  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen
  • Biomarkers
  • Biomarkers, Tumor
  • ramucirumab

Associated data