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

• Published in: Nature communications Vol. 13; no. 1; p. 1878
• Main Authors: van der Heijden, Michiel S., Powles, Thomas, Petrylak, Daniel, de Wit, Ronald, Necchi, Andrea, Sternberg, Cora N., Matsubara, Nobuaki, Nishiyama, Hiroyuki, Castellano, Daniel, Hussain, Syed A., Bamias, Aristotelis, Gakis, Georgios, Lee, Jae-Lyun, Tagawa, Scott T., Vaishampayan, Ulka, Aragon-Ching, Jeanny B., Eigl, Bernie J., Hozak, Rebecca R., Rasmussen, Erik R., Xia, Meng Summer, Rhodes, Ryan, Wijayawardana, Sameera, Bell-McGuinn, Katherine M., Aggarwal, Amit, Drakaki, Alexandra
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06-04-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/51; 38/39; 631/67/1857; 631/67/589/1336; 692/53/2423; Angiogenesis; Antibodies, Monoclonal, Humanized; Apoptosis; B7-H1 Antigen - analysis; Biomarkers; Biomarkers, Tumor; Bladder cancer; Cancer; Carcinoma, Transitional Cell - pathology; Cell death; Humanities and Social Sciences; Humans; Immunohistochemistry; Immunotherapy; Monoclonal antibodies; multidisciplinary; Patients; PD-L1 protein; Phenotypes; Platinum; Ramucirumab; Science; Science (multidisciplinary); Survival; Targeted cancer therapy; Transcriptomes; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - pathology; Urothelial cancer; Urothelial carcinoma
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-29441-y

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.
Identification of biomarkers to stratify patients who might benefit from treatment is needed to optimize targeted therapies. Here, based on an analysis of the RANGE trial (NCT02426125), the authors report potentially predictive biomarkers for survival benefit in patients with platinum-refractory advanced urothelial carcinoma treated with the anti-VEGFR2 monoclonal antibody ramucirumab.