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

Author

Listed:
  • Michiel S. Heijden

    (The Netherlands Cancer Institute)

  • Thomas Powles

    (Queen Mary University of London)

  • Daniel Petrylak

    (Yale New Haven Hospital)

  • Ronald Wit

    (Erasmus MC Cancer Institute)

  • Andrea Necchi

    (Vita-Salute San Raffaele University and IRCCS San Raffaele Hospital)

  • Cora N. Sternberg

    (Meyer Cancer Center, New York-Presbyterian Hospital)

  • Nobuaki Matsubara

    (National Cancer Center Hospital East)

  • Hiroyuki Nishiyama

    (University of Tsukuba)

  • Daniel Castellano

    (Hospital Universitario 12 de Octubre)

  • Syed A. Hussain

    (University of Sheffield, Department of Oncology and Metabolism)

  • Aristotelis Bamias

    (National and Kapodistrian University of Athens)

  • Georgios Gakis

    (University Hospital of Würzburg)

  • Jae-Lyun Lee

    (Urologic Cancer Center)

  • Scott T. Tagawa

    (Weill Cornell Medical College, Department of Genitourinary Oncology)

  • Ulka Vaishampayan

    (University of Michigan Ann Arbor)

  • Jeanny B. Aragon-Ching

    (Inova Schar Cancer Institute)

  • Bernie J. Eigl

    (BC Cancer)

  • Rebecca R. Hozak

    (Eli Lilly and Company)

  • Erik R. Rasmussen

    (Eli Lilly and Company)

  • Meng Summer Xia

    (Eli Lilly and Company)

  • Ryan Rhodes

    (Eli Lilly and Company)

  • Sameera Wijayawardana

    (Eli Lilly and Company)

  • Katherine M. Bell-McGuinn

    (Eli Lilly and Company)

  • Amit Aggarwal

    (Eli Lilly and Company)

  • Alexandra Drakaki

    (Division of Hematology and Oncology, UCLA)

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.

Suggested Citation

  • Michiel S. Heijden & Thomas Powles & Daniel Petrylak & Ronald Wit & Andrea Necchi & Cora N. Sternberg & Nobuaki Matsubara & Hiroyuki Nishiyama & Daniel Castellano & Syed A. Hussain & Aristotelis Bamia, 2022. "Predictive biomarkers for survival benefit with ramucirumab in urothelial cancer in the RANGE trial," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29441-y
    DOI: 10.1038/s41467-022-29441-y
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    References listed on IDEAS

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    1. Brian D. Robinson & Panagiotis J. Vlachostergios & Bhavneet Bhinder & Weisi Liu & Kailyn Li & Tyler J. Moss & Rohan Bareja & Kyung Park & Peyman Tavassoli & Joanna Cyrta & Scott T. Tagawa & David M. N, 2019. "Upper tract urothelial carcinoma has a luminal-papillary T-cell depleted contexture and activated FGFR3 signaling," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    2. Roy S. Herbst & Jean-Charles Soria & Marcin Kowanetz & Gregg D. Fine & Omid Hamid & Michael S. Gordon & Jeffery A. Sosman & David F. McDermott & John D. Powderly & Scott N. Gettinger & Holbrook E. K. , 2014. "Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients," Nature, Nature, vol. 515(7528), pages 563-567, November.
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