| Title | Predictive biomarkers for survival benefit with ramucirumab in urothelial cancer in the RANGE trial. |
| Publication Type | Journal Article |
| Year of Publication | 2022 |
| Authors | 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-L, Tagawa ST, Vaishampayan U, Aragon-Ching JB, Eigl BJ, Hozak RR, Rasmussen ER, Xia MSummer, Rhodes R, Wijayawardana S, Bell-McGuinn KM, Aggarwal A, Drakaki A |
| Journal | Nat Commun |
| Volume | 13 |
| Issue | 1 |
| Pagination | 1878 |
| Date Published | 2022 Apr 06 |
| ISSN | 2041-1723 |
| Keywords | Antibodies, Monoclonal, Humanized, B7-H1 Antigen, Biomarkers, Biomarkers, Tumor, Carcinoma, Transitional Cell, Humans, Urinary Bladder Neoplasms |
| 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. |
| DOI | 10.1038/s41467-022-29441-y |
| Alternate Journal | Nat Commun |
| PubMed ID | 35388003 |
| PubMed Central ID | PMC8987042 |