TY - JOUR
T1 - Predictive biomarkers for survival benefit with ramucirumab in urothelial cancer in the RANGE trial
AU - van der Heijden, Michiel S.
AU - Powles, Thomas
AU - Petrylak, Daniel
AU - de Wit, Ronald
AU - Necchi, Andrea
AU - Sternberg, Cora N.
AU - Matsubara, Nobuaki
AU - Nishiyama, Hiroyuki
AU - Castellano, Daniel
AU - Hussain, Syed A.
AU - Bamias, Aristotelis
AU - Gakis, Georgios
AU - Lee, Jae-Lyun
AU - Tagawa, Scott T.
AU - Vaishampayan, Ulka
AU - Aragon-Ching, Jeanny B.
AU - Eigl, Bernie J.
AU - Hozak, Rebecca R.
AU - Rasmussen, Erik R.
AU - Xia, Meng Summer
AU - Rhodes, Ryan
AU - Wijayawardana, Sameera
AU - Bell-McGuinn, Katherine M.
AU - Aggarwal, Amit
AU - Drakaki, Alexandra
N1 - Funding Information: This study was funded by Eli Lilly and Company. The funder provided support in the form of salaraies for authors (RRH, ERR, MSX, RR, SW, KMB-M, and AA), design of study, data collection, data analysis, decision to publish, and preparation of the manuscript. We thank the patients, their families, and the study personnel across all sites for participating in the RANGE trial. We also thank Decipher Biosciences for performing the gene expression profiling and molecular subtyping of the tumor samples, as well as insightful discussions (Elai Davicioni and Ewan Gibb). Kristi Gruver and Susan Whitman of Eli Lilly and Company provided project management support. Erika Wittchen and Antonia Baldo of Syneos Health provided medical writing and editorial support, funded by Eli Lilly and Company. Funding Information: This study was funded by Eli Lilly and Company. The funder provided support in the form of salaraies for authors (RRH, ERR, MSX, RR, SW, KMB-M, and AA), design of study, data collection, data analysis, decision to publish, and preparation of the manuscript. We thank the patients, their families, and the study personnel across all sites for participating in the RANGE trial. We also thank Decipher Biosciences for performing the gene expression profiling and molecular subtyping of the tumor samples, as well as insightful discussions (Elai Davicioni and Ewan Gibb). Kristi Gruver and Susan Whitman of Eli Lilly and Company provided project management support. Erika Wittchen and Antonia Baldo of Syneos Health provided medical writing and editorial support, funded by Eli Lilly and Company. Publisher Copyright: © 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85127624381&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-022-29441-y
DO - https://doi.org/10.1038/s41467-022-29441-y
M3 - Article
C2 - 35388003
SN - 2041-1723
VL - 13
SP - 1878
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1878
ER -