- van der Heijden, Michiel S;
- Powles, Thomas;
- Petrylak, Daniel;
- de Wit, Ronald;
- Necchi, Andrea;
- Sternberg, Cora N;
- Matsubara, Nobuaki;
- Nishiyama, Hiroyuki;
- Castellano, Daniel;
- Hussain, Syed A;
- Bamias, Aristotelis;
- Gakis, Georgios;
- Lee, Jae-Lyun;
- Tagawa, Scott T;
- Vaishampayan, Ulka;
- Aragon-Ching, Jeanny B;
- Eigl, Bernie J;
- Hozak, Rebecca R;
- Rasmussen, Erik R;
- Xia, Meng Summer;
- Rhodes, Ryan;
- Wijayawardana, Sameera;
- Bell-McGuinn, Katherine M;
- Aggarwal, Amit;
- Drakaki, Alexandra
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.