Authors: Michiel S. van der Heijden, Thomas Powles, Daniel Petrylak, Ronald de Wit, Andrea Necchi, Cora N. Sternberg, Nobuaki Matsubara, Hiroyuki Nishiyama, Daniel Castellano, Syed A. Hussain, Aristotelis Bamias, Georgios Gakis, Jae-Lyun Lee, Scott T. Tagawa, Ulka Vaishampayan, Jeanny B. Aragon-Ching, Bernie J. Eigl, Rebecca R. Hozak, Erik R. Rasmussen, Meng Summer Xia, Ryan Rhodes, Sameera Wijayawardana, Katherine M. Bell-McGuinn, Amit Aggarwal, Alexandra Drakaki
Published: 2022-04-06
DOI: 10.1038/s41467-022-29441-y
Source: Full article
AbstractThe 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.