Predictive biomarkers for survival benefit with ramucirumab in urothelial cancer in the RANGE trial.
Michiel S Van Der HeijdenThomas PowlesDaniel PetrylakRonald de WitAndrea NecchiCora N SternbergNobuaki MatsubaraHiroyuki NishiyamaDaniel CastellanoSyed Anwer HussainAristotelis BamiasGeorgios GakisJae-Lyun LeeScott T TagawaUlka VaishampayanJeanny B Aragon-ChingBernhard J EiglRebecca R HozakErik R RasmussenMeng Summer XiaRyan RhodesSameera WijayawardanaKatherine M Bell-McGuinnAmit AggarwalAlexandra DrakakiPublished in: Nature communications (2022)
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.
Keyphrases
- endothelial cells
- vascular endothelial growth factor
- monoclonal antibody
- end stage renal disease
- clinical trial
- ejection fraction
- wound healing
- chronic kidney disease
- randomized controlled trial
- squamous cell carcinoma
- machine learning
- peritoneal dialysis
- study protocol
- electronic health record
- papillary thyroid
- open label
- phase iii
- data analysis