Journal
EUROPEAN UROLOGY
Volume 75, Issue 6, Pages 961-964Publisher
ELSEVIER
DOI: 10.1016/j.eururo.2019.02.017
Keywords
Bladder cancer; Subtypes; Immunotherapy; Anti-PD-L1 antibody; Neuronal; Urothelial cancer; The Cancer Genome Atlas; TP53; RB1
Categories
Funding
- AstraZeneca
- Janssen
- Takeda
- Bioclin
- Pfizer
- MSD
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Analysis of the IMvigor 210 trials involving patients with platinum-refractory or cisplatin-ineligible urothelial carcinoma who were treated with the PD-L1 inhibitor atezolizumab identified a resistance signature as an immune biomarker. Transcriptome profiling of 368 tumor samples from this trial revealed that the genomically unstable Lund subtype classification was associated with the best response. We developed and applied a novel single-patient subtype classifier based on The Cancer Genome Atlas 2017 expression-based molecular subtypes. We identified 11 patients with a neuronal subtype, with a 100% response rate in eight confirmed cases (2 complete response, 6 partial response), and 72% overall, including 3/11 patients with an unconfirmed response. The survival probability was extraordinarily high for the neuronal subtype, which represents a high-risk cohort with advanced disease, and may be secondary to low levels of TGF beta expression and high mutation/neoantigen burden. Patient summary: We describe a methodology for genomic classification of an individual patient's bladder cancer tumor and have identified a subtype that is associated with a high response rate to immunotherapy. This is an important step forward in identifying the right treatment for the right patient, which is the goal of personalized precision medicine. (C) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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