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

Michiel S. Heijden (), Thomas Powles, Daniel Petrylak, Ronald 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 and Alexandra Drakaki
Additional contact information
Michiel S. Heijden: The Netherlands Cancer Institute
Thomas Powles: Queen Mary University of London
Daniel Petrylak: Yale New Haven Hospital
Ronald Wit: Erasmus MC Cancer Institute
Andrea Necchi: Vita-Salute San Raffaele University and IRCCS San Raffaele Hospital
Cora N. Sternberg: Meyer Cancer Center, New York-Presbyterian Hospital
Nobuaki Matsubara: National Cancer Center Hospital East
Hiroyuki Nishiyama: University of Tsukuba
Daniel Castellano: Hospital Universitario 12 de Octubre
Syed A. Hussain: University of Sheffield, Department of Oncology and Metabolism
Aristotelis Bamias: National and Kapodistrian University of Athens
Georgios Gakis: University Hospital of Würzburg
Jae-Lyun Lee: Urologic Cancer Center
Scott T. Tagawa: Weill Cornell Medical College, Department of Genitourinary Oncology
Ulka Vaishampayan: University of Michigan Ann Arbor
Jeanny B. Aragon-Ching: Inova Schar Cancer Institute
Bernie J. Eigl: BC Cancer
Rebecca R. Hozak: Eli Lilly and Company
Erik R. Rasmussen: Eli Lilly and Company
Meng Summer Xia: Eli Lilly and Company
Ryan Rhodes: Eli Lilly and Company
Sameera Wijayawardana: Eli Lilly and Company
Katherine M. Bell-McGuinn: Eli Lilly and Company
Amit Aggarwal: Eli Lilly and Company
Alexandra Drakaki: Division of Hematology and Oncology, UCLA

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-29441-y

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