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.
Resources from the same session
3128 - Systemic bevacizumab for the treatment of recurrent respiratory papillomatosis: A retrospective analysis from an academic tertiary care center
Presenter: Sumita Trivedi
Session: Poster Display session 3
Resources:
Abstract
1242 - Monalizumab in combination with cetuximab in patients (pts) with recurrent or metastatic (R/M) head and neck cancer (SCCHN) previously treated or not with PD-(L)1 inhibitors (IO): 1-year survival data.
Presenter: Roger Cohen
Session: Poster Display session 3
Resources:
Abstract
4703 - Updated results of a phase II study evaluating accelerator-based boron neutron capture therapy (AB-BNCT) with borofalan(10B) (SPM-011) in recurrent squamous cell carcinoma (R-SCC-HN) and recurrent and locally advanced non-SCC (R/LA-nSCC-HN) of the head and neck
Presenter: Katsumi Hirose
Session: Poster Display session 3
Resources:
Abstract
3638 - Phase 3 KEYNOTE-048 Study of First-Line (1L) Pembrolizumab (P) for Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC): Asia vs Non-Asia Subgroup (subgrp) Analysis
Presenter: Makoto Tahara
Session: Poster Display session 3
Resources:
Abstract
2954 - Integrated data review evaluating safety, pharmacokinetics (PK) and immunogenicity of RM-1929 photoimmunotherapy (PIT) in subjects with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC).
Presenter: Jennifer Johnson
Session: Poster Display session 3
Resources:
Abstract
3629 - First line versus second line immunotherapy in recurrent/metastatic squamous cell carcinoma of the head and neck
Presenter: Caroline Even
Session: Poster Display session 3
Resources:
Abstract
767 - Sensitizing HRAS overexpressing head and neck squamous cell carcinoma (HNSCC) to chemotherapy
Presenter: Theodoros Rampias
Session: Poster Display session 3
Resources:
Abstract
4985 - A Single-Arm, Open-Label, Multicenter, Phase IIIb Clinical Trial with Nivolumab in Subjects with Recurrent or Metastatic Platinum-refractory Squamous Cell Carcinoma of the Head and Neck.
Presenter: Paolo Bossi
Session: Poster Display session 3
Resources:
Abstract
1564 - Long-term Results of Phase 2 Trial of Reduced Modified Clinical Target Volume in Low-risk Nasopharyngeal Carcinoma Treated with Intensity Modulated Radiotherapy
Presenter: Jingjing Miao
Session: Poster Display session 3
Resources:
Abstract
3356 - To compare two oral mucosa contouring methods in predicting acute oral mucocitis in nasopharyngeal carcinoma treated with helical tomotherapy
Presenter: Yuan-Yuan Chen
Session: Poster Display session 3
Resources:
Abstract