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Poster Display session 3

3110 - Prognostic role of FGFR Mutations and FGFR mRNA expression in metastatic urothelial cancer treated with anti-PD(L1) inhibitors in first and second line setting

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Tumour Site

Urothelial Cancer

Presenters

Florian Roghmann

Citation

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

Authors

F. Roghmann1, R. Wirtz2, J. Jarczyk3, M.C. Kriegmair3, T.S. Worst3, D. Sikic4, S. Wach4, H. Taubert4, B. Wullich4, V. Weyerer5, R. Stoehr5, F. Zengerling6, C. Bolenz6, J. Breyer7, M. Burger7, S. Porubsky8, A. Hartmann9, P. Erben10, M. Eckstein5, H. Juette11

Author affiliations

  • 1 Urologic Department Of The Ruhr - University Bochum, Marienhospital Herne, 44625 - Herne/DE
  • 2 On Behalf Of The Bridge-consortium E.v., STRATIFYER Molecular Pathology GmbH, Cologne, 50935 - Cologne/DE
  • 3 Urology, University Hospital Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, 68159 - Mannheim/DE
  • 4 Department Of Urology And Pediatric Urology, Universitätsklinik Erlangen, 91054 - Erlangen/DE
  • 5 Institute Of Pathology, Universitätsklinik Erlangen, 91054 - Erlangen/DE
  • 6 Department Of Urology, University Hospital Ulm, University of Ulm, Ulm, 89081 - Ulm/DE
  • 7 Department Of Urology, University of Regensburg, Regensburg/DE
  • 8 Pathology, Department of Pathology, University Hospital Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Mannheim/DE
  • 9 Institute Of Pathology, Universitätsklinik Erlangen, 91052 - Erlangen/DE
  • 10 Department Of Urology Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim/DE
  • 11 Department Of Pathology, Ruhr University Bochum, Bochum/DE

Resources

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Abstract 3110

Background

In the era of individualized oncological therapy in bladder cancer, FGFR3 mutations, FGFR2/FGFR3 gene fusions and FGFR mRNA expression as potential oncological targets and their association to anti-PD-1/anti-PD-L1 (IO) treatment outcomes in patients with advanced urothelial cancer of the bladder (UCB) were studied in a German patient cohort.

Methods

Within a cohort of 72 patients with metastatic UCB from 5 academic centers in Germany (collected between 2016 and 2018) FGFR3 mutations, FGFR2 and FGFR3 gene fusions as well as FGFR expression in formalin-fixed, paraffin embedded (FFPE) tumour samples and their association to survival were examined using SNaPshot PCR, RT-qPCR as well as Next Generation Sequencing. Statistical analyses comprised Kaplan-Meier survival analyses, Spearman rank correlations, non-parametric testing.

Results

In 17% of all patients FGFR3 mutations or gene fusions could be detected. Patients with FGFR3 alterations did not have better outcome after immunoncology (IO) treatment, but rather tended to have inferior disease specific survival. All alterations of FGFR3 resulted in overexpression of FGFR3 mRNA. Combination of FGFR mutation analysis and FGFR mRNA assessment improved IO outcome prediction. Overexpression of FGFR3 mRNA was negatively associated with PDL1 expression (mRNA and protein level). High FGFR2 mRNA expression in primary tumors predicted better disease specific survival of UCB patients receiving IO therapy, whereas high FGFR3 mRNA expression was associated with tumor specific death in patients exhibiting of low FGFR2 mRNA expressions (p < 0.05). This high risk group of UCB patients exhibiting high mRNA levels FGFR3 comprises 40% of the total cohort.

Conclusions

The assessment of FGFR mRNA by standardized RT-qPCR identified a high risk UCB patient cohort, which does have inferior disease specific survival despite IO treatment and does overexpress FGFR3 mRNA. The assessment of FGFR mRNA levels by using this standardized, locally applicable FGFR test system could identify an FGFR inhibitor target population with poor response to IO treatment which is twice the size as currently detected by FGFR genomic alterations alone.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

BRIDGE Consortium e.V.

Funding

Janssen.

Disclosure

F. Roghmann: Advisory / Consultancy: Janssen; Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: Ipsen. All other authors have declared no conflicts of interest.

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