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| Status |
Public on Mar 14, 2022 |
| Title |
Predictive biomarkers for survival benefit with ramucirumab in urothelial cancer in the RANGE trial |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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 suggest 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.
Please note that the RANGE clinical trial data generated in this study have been deposited at www.vivli.org. RANGE clinical trial data are available under restricted access to protect patient privacy, and access can be obtained by submitting a request. For details on submitting a request, see the instructions provided at www.vivli.org. For specific study details, see here: https://search.vivli.org/?search=NCT02426125.
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| Overall design |
RNA was isolated from tumor sample specimens from 394 patients with MIBC in the RANGE Phase 3 cliinical trial and whole transcriptome profiling was performed. Samples were classified according to four published molecular subtyping methods.
Please note that CEL files contain the 'Decipher' string for chp information. The array data (i.e. CEL files) were generated for Eli Lilly by Decipher Biosciences (as part of a service contract to perform gene expression profiling and apply their proprietary bladder cancer molecular subtype classifier to these n=394 patient samples) and the 'HuEx-1_0-st' array was positioned as their proprietary 'Decipher' array.
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| Contributor(s) |
van der Heijden MS, Powles T, Petrylak D, de Wit R, Necchi A, Sternberg CN, Matsubara N, Nishiyama H, Castellano D, Hussain SA, Bamias A, Gakis G, Lee J, Tagawa ST, Vaishampayan U, Aragon-Ching JB, Eigl BJ, Hozak RR, Rasmussen ER, Xia MS, Rhodes R, Wijayawardana S, Bell-McGuinn KM, Aggarwal A, Drakaki A |
| Citation(s) |
35388003 |
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| Submission date |
Mar 09, 2022 |
| Last update date |
Apr 27, 2022 |
| Contact name |
Erik Roy Rasmussen |
| E-mail(s) |
[email protected]
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| Phone |
6315251757
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| Organization name |
Eli Lilly
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| Street address |
430 East 29th Street
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10016 |
| Country |
USA |
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| Platforms (1) |
| GPL22995 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version, custom CDF] |
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| Samples (394)
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| Relations |
| BioProject |
PRJNA814304 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE198269_RAW.tar |
7.7 Gb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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