Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 3

2108 - Biomarker analyses of ramucirumab in patients with platinum refractory urothelial cancer from RANGE, a global, randomized, double-blind, phase 3 study.

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Tumour Site

Urothelial Cancer

Presenters

Michiel Van der Heijden

Citation

Annals of Oncology (2019) 30 (suppl_5): v356-v402. 10.1093/annonc/mdz249

Authors

M.S. Van der Heijden1, T.B. Powles2, D.P. Petrylak3, R. de Wit4, K.N. Chi5, A. Necchi6, C.N. Sternberg7, N. Matsubara8, H. Nishiyama9, D. Castellano Gauna10, S.A. Hussain11, A. Bamias12, R.R. Hozak13, R. Rhodes13, M.S. Xia13, E. Rasmussen13, A. Aggarwal13, S.R. Wijayawardana13, K. Bell-McGuinn14, A. Drakaki15

Author affiliations

  • 1 -, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, 1072 - Amsterdam/NL
  • 2 Barts Cancer Institute, Queen Mary University of London, EC1A 7BE - London/GB
  • 3 -, Yale Cancer Center, 06510 - New Haven/US
  • 4 -, Erasmus MC Cancer Institute, 3075EA - Rotterdam/NL
  • 5 -, British Columbia Cancer Agency, V5Z 4E6 - Vancouver/CA
  • 6 -, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 7 -, Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York-Presbyterian Hospital, 00156 - New York/US
  • 8 -, National Cancer Center Hospital East, Chiba/JP
  • 9 -, University of Tsukuba, Tsukuba/JP
  • 10 -, University Hospital 12 de Octubre, 28041 - Madrid/ES
  • 11 Department Of Oncology And Metabolism, University of Sheffield, Sheffield/GB
  • 12 -, National and Kapodistrian University of Athens, 11527 - Athens/GR
  • 13 -, Eli Lilly and Company, Indianapolis/US
  • 14 -, Eli Lilly and Company, 46285 - Indianapolis/US
  • 15 Division Of Hematology And Oncology, David Geffen School of Medicine, UCLA, 90095 - Los Angeles/US

Resources

Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 2108

Background

RANGE previously reported positive progression-free survival1 and a trend towards improved overall survival (OS)2 in ramucirumab (RAM) treated patients. Exploratory biomarker analysis of efficacy by programmed death-ligand 1 (PD-L1) expression revealed a hazard ratio (HR) for OS of 0.519, p = 0.0048 in patients with a PD-L1 combined positive score (CPS)≥10 compared to HR of 0.999, p = 0.9955 in patients with a PD-L1 CPS<10. We aim to understand prognostic and predictive factors related to survival outcomes in RANGE, and to identify patients who may benefit from RAM therapy using PD-L1 immunohistochemistry and gene expression analysis, defining molecular subtypes, and tumour microenvironment signatures.

Methods

Archival tumour specimens that met assay stability requirements (238/530 ITT patients in RANGE) were analyzed with the 22C3 PD-L1 antibody with CPS based on tumour cell (TC) and immune cell (IC) staining. RNA expression analysis on archival tumour tissue (394/530 ITT patients) was done by GenomeDx (RNA microarray)3. PD-L1 groups, urothelial carcinoma molecular subtypes, and immune4 and stromal phenotypes5 were determined and analyzed for association with OS outcome.

Results

Overall, RAM had the greatest improvement in OS in patients with TC ≥ 1, IC ≥ 4 or CPS≥10 PD-L1 status. OS was also more improved in patients with basal subtypes, with considerable overlap noted between basal subtypes and TC ≥ 1, IC ≥ 4, or CPS ≥10 PD-L1 status. In the subgroup with both basal/basal claudin-low subtype and CPS≥10 PD-L1 status, median OS was 9.2 months with RAM and 6.0 months with placebo (stratified hazard ratio 0.47; 95% confidence interval: 0.27-0.84, p = 0.01, n = 79).

Conclusions

Our analysis suggested significant improvement in OS in RAM treated patients with platinum refractory urothelial carcinoma, and with both basal subtype and positive PD-L1 status. References: 1Petrylak et al, Lancet 2017; 390:2266-77; 2Petrylak et al, Ann Oncol 2018; 29:viii304-5; 3Seiler et al, Eur Urol 2017; 72:544-54; 4Charoentong et al, Cell Rep 2017; 18:248-62; 5Uhlik et al Cancer Res 2016; 76:2573-86.

Clinical trial identification

NCT02426125.

Editorial acknowledgement

Lisa Cossens and Antonia Baldo of Syneos Health, funded by Eli Lilly and Company.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

T.B. Powles: Research grant / Funding (self), Personal fees: Roche; Research grant / Funding (self), Personal fees: AZ; Licensing / Royalties, Personal fees: Merck; Licensing / Royalties, Personal fees: Eli Lilly and Company; Licensing / Royalties, Personal fees: BMS; Licensing / Royalties, Personal fees: Pfizer. D.P. Petrylak: Research grant / Funding (self): Eli Lilly and Company; Licensing / Royalties, Personal fees: Bayer; Research grant / Funding (self), Licensing / Royalties, Personal fees: Bellicum; Research grant / Funding (self), Licensing / Royalties, Personal fees: Dendreon; Research grant / Funding (self), Licensing / Royalties, Personal fees: Sanofi Aventis; Research grant / Funding (self), Licensing / Royalties, Personal fees: Johnson and Johnson; Licensing / Royalties, Personal fees: Exelixis; Licensing / Royalties, Personal fees: Ferring; Research grant / Funding (self), Licensing / Royalties, Personal fees: Millineum; Licensing / Royalties, Personal fees: Medivation; Licensing / Royalties, Personal fees: Pfizer; Research grant / Funding (self), Licensing / Royalties, Personal fees: Roche Laboratories; Research grant / Funding (self), Licensing / Royalties, Personal fees: Tyme Pharmaceuticals; Research grant / Funding (self): Oncogenix; Research grant / Funding (self): Progenics; Research grant / Funding (self): Merck; Research grant / Funding (self): Agensys. R. de Wit: Licensing / Royalties: Eli Lilly and Company; Licensing / Royalties: Merck; Licensing / Royalties: Roche; Licensing / Royalties: Sanofi. K.N. Chi: Research grant / Funding (institution): Eli Lilly and Company. A. Necchi: Research grant / Funding (self), Licensing / Royalties, Non-remunerated activity/ies: Roche; Licensing / Royalties: Merck; Licensing / Royalties: AstraZeneca; Licensing / Royalties: Seattle Genetics; Licensing / Royalties: Bayer. C.N. Sternberg: Licensing / Royalties: Eli Lilly and Company; Licensing / Royalties: BMS; Licensing / Royalties: Merck/Pfizer; Licensing / Royalties: Clovis. S.A. Hussain: Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): MSD; Research grant / Funding (institution): BMS. A. Bamias: Licensing / Royalties: AstraZeneca; Licensing / Royalties: BMS; Research grant / Funding (self), Licensing / Royalties: Roche. M.S. Xia: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. E. Rasmussen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company.A. Aggarwal: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. S.R. Wijayawardana: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. K. Bell-McGuinn: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.