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.
Nature communications. 2022 Apr 06*** epublish ***
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
The Netherlands Cancer Institute, Amsterdam, The Netherlands. ., Barts Cancer Institute, Queen Mary University of London, London, UK., Smilow Cancer Hospital at Yale New Haven, Yale New Haven Hospital, New Haven, CT, USA., Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Vita-Salute San Raffaele University and IRCCS San Raffaele Hospital, Milan, Italy., Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, Meyer Cancer Center, New York-Presbyterian Hospital, New York, NY, USA., National Cancer Center Hospital East, Chiba, Japan., University of Tsukuba, Tsukuba, Ibaraki, Japan., Hospital Universitario 12 de Octubre, Madrid, Spain., University of Sheffield, Department of Oncology and Metabolism, Sheffield, UK., National and Kapodistrian University of Athens, Athens, Greece., University Hospital of Würzburg, Würzburg, Germany., Asan Medical Center, Urologic Cancer Center, Seoul, South Korea., Weill Cornell Medical College, Department of Genitourinary Oncology, New York, NY, USA., University of Michigan Ann Arbor, Ann Arbor, MI, USA., Inova Schar Cancer Institute, Fairfax, VA, USA., BC Cancer, Vancouver, BC, Canada., Eli Lilly and Company, Indianapolis, IN, USA., Eli Lilly and Company, New York, NY, USA., David Geffen School of Medicine, Division of Hematology and Oncology, UCLA, Los Angeles, CA, USA.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/35388003