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

2657 - Prognostic immunoprofiling of muscle invasive bladder cancer (MIBC) patients in a multicentre setting

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Translational Research

Tumour Site

Urothelial Cancer

Presenters

Katharina Nekolla

Citation

Annals of Oncology (2019) 30 (suppl_5): v25-v54. 10.1093/annonc/mdz239

Authors

K. Nekolla1, N. Brieu1, C.G. Gavriel2, M. Widmaier1, A. Budco1, D. Medrikova1, I. Kanchev1, M. Testori1, J. Chan1, P. Dundee3, P. Anderson3, N. Lawrentschuk4, L. Wong5, P. Phan6, P. Gibbs6, D.J. Harrison2, M. Baehner1, P.D. Caie2, B. Tran6, G. Schmidt1

Author affiliations

  • 1 R&d, Definiens AG, 80636 - Munich/DE
  • 2 School Of Medicine, University of St Andrews, KY16 9TF - St Andrews/GB
  • 3 Department Of Urology, Royal Melbourne Hospital, 3050 - Parkville/AU
  • 4 Department Of Surgical Oncology, Peter MacCallum Cancer Centre, 3000 - Melbourne/AU
  • 5 Department Of Urology, St Vincent’s Hospital Melbourne, 3065 - Fitzroy/AU
  • 6 Division Of Personalised Oncology, The Walter and Eliza Hall Institute of Medical Research, 3052 - Parkville/AU

Resources

Login to access the resources on OncologyPRO.

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

Abstract 2657

Background

Introduction of checkpoint inhibitors (anti PD-1/PD-L1) have resulted in improved survival for bladder cancer patients, however, only a subset will benefit. The utility of PD-L1 expression as a prognostic or predictive biomarker is limited, motivating the search for more robust biomarkers. Here, we examined the prognostic value of densities of PD-L1, CD3, CD8 or CD68 positive cells and studied the reproducibility of the findings across two patient cohorts in a multi-assay and multicentre setting.

Methods

MIBC specimens (T stage 2/3) from two patient cohorts collected at Melbourne, Australia (n = 39) and University of St Andrews, UK (n = 63) were studied. Two consecutive slides were stained with a brightfield immunohistochemistry or an immunofluorescence assay in the first and second cohorts, respectively. The densities of positive cells within the tumour core were determined using assay-specific image analysis algorithms. Within each cohort, the prognostic value of each cell density was assessed using univariate and multivariate Cox regression including age, T stage, N stage and adjuvant chemotherapy as covariates.

Results

The Melbourne cohort is slightly older, with a poorer prognosis and a higher proportion of N2/N3 disease compared to the St Andrews cohort. Univariate and multivariate analyses identified the density of CD8 positive cells as an important prognostic factor across both cohorts (p < 0.05). PD-L1 is significant in the St Andrews cohort and trends towards significance (p < 0.1) in the Melbourne cohort, whilst the reverse is seen with CD3. The significance level of CD68 cannot be reproduced across cohorts. Cohort statistics, hazard ratios and p values from univariate and multivariate survival analysis. .p < 0.1, *p<0.05, **p<0.01Table: 159P

Cohort 1: MelbourneCohort 2: St Andrews
Median age71.6466
Median survival time (months)23.7 - Overall32.57 - Disease Related
T stage
T216 (41%)26 (41%)
T323 (59%)37 (59%)
N stage
N13 (8%)52 (88%)
N28 (20%)7 (11%)
N328 (72%)0 (0%)
Univariate Cox regression
CD8HR 0.93 (0.88 0.98), p = 0.007 **HR 0.90 (0.83 0.97), p = 0.005 **
PD-L1HR 0.97 (0.94 1.00), p = 0.065 .HR 0.86 (0.75 0.98), p = 0.023 *
CD3HR 0.92 (0.87 0.97), p = 0.003 **HR 0.92 (0.87 0.98), p = 0.010 *
CD68HR 0.93 (0.88 0.99), p = 0.025 *HR 0.97 (0.93 1.00), p = 0.088 .
Multivariate Cox regression
CD8HR 0.92 (0.88 0.97), p = 0.003 **HR 0.92 (0.86 0.99), p = 0.029 *
PD-L1HR 0.96 (0.92 1.00), p = 0.053 .HR 0.84 (0.74 0.97), p = 0.015 *
CD3HR 0.90 (0.85 0.95), p = 0.0004**HR 0.94 (0.88 1.00), p = 0.060 .
CD68HR 0.92 (0.86 0.99), p = 0.023 *HR 0.98 (0.94 1.02), p = 0.294

Conclusions

Our multicentre and multi-assay study suggests that the density of CD8 positive cells in the tumour core is a robust prognostic factor in MIBC. Further investigation of PD-L1 and CD3 cell density is warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Definiens AG; The Walter and Eliza Hall Institute of Medical Research; University of St Andrews.

Funding

Definiens AG.

Disclosure

K. Nekolla: Full / Part-time employment, Definiens is a full subsidiary of AstraZeneca: Definiens AG. N. Brieu: Full / Part-time employment, Definiens is a full subsidiary of AstraZeneca: Definiens AG. C.G. Gavriel: Research grant / Funding (self), Definiens is a full subsidiary of AstraZeneca: Definiens AG. M. Widmaier: Full / Part-time employment, Definiens is a full subsidiary of AstraZeneca: Definiens AG. A. Budco: Full / Part-time employment, Definiens is a full subsidiary of AstraZeneca: Definiens AG. D. Medrikova: Full / Part-time employment, Definiens is a full subsidiary of AstraZeneca: Definiens AG. I. Kanchev: Full / Part-time employment, Definiens is a full subsidiary of AstraZeneca: Definiens AG. M. Testori: Full / Part-time employment, Definiens is a full subsidiary of AstraZeneca: Definiens AG. J. Chan: Full / Part-time employment, Definiens is a full subsidiary of AstraZeneca: Definiens AG. D.J. Harrison: Advisory / Consultancy, Member: Scientific Advisory Board: Definiens AG; Full / Part-time employment: NuCana plc; Leadership role, Director: Industrial Centre for AI Research in Digital Diagnostics. M. Baehner: Full / Part-time employment, Definiens is a full subsidiary of AstraZeneca: Definiens AG. P.D. Caie: Research grant / Funding (institution): Definiens AG. B. Tran: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Astellas; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Non-remunerated activity/ies: Janssen-Cilag; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy: Tolmar; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Ipsen; Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Research grant / Funding (self): Pfizer; Research grant / Funding (self), Research grant / Funding (institution): Servier; Research grant / Funding (institution): Aslan; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Akeso; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Aptevo; Leadership role, Chair - GU Tumour Group: Cancer Trials Australia; Leadership role, Chair - Germ Cell Tumour Subcommittee, Member - Scientific Advisory Committee: ANZUP; Leadership role, Member - Scientific Advisory Committee: Biogrid; Leadership role, Member - Scientific Advisory Committee: Parkville Cancer Clinical Trials Unit; Leadership role, Co-Chair - Molecular Tumour Board: Victorian Comprehensive Cancer Centre. G. Schmidt: Full / Part-time employment, Definiens is a full subsidiary of AstraZeneca: Definiens AG; Shareholder / Stockholder / Stock options: AstraZeneca; Licensing / Royalties, Royalities "Tissue Phenomics" ISBN 9789814774888: Pan Stanford Publishing. 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.