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
3290 - Identification of meningioma patients in high risk of tumor recurrence using microRNA profiling
Presenter: Josef Srovnal
Session: Poster Display session 3
Resources:
Abstract
2477 - Antecedent of cancer and mortality after the first ST segment elevation acute myocardial infarction treated with primary coronary angioplasty. A prospective cohort study
Presenter: Irene Sillero
Session: Poster Display session 3
Resources:
Abstract
1894 - Genomic characterisation of locally advanced pancreatic adenocarcinoma
Presenter: Sarah Picardo
Session: Poster Display session 3
Resources:
Abstract
3280 - Comparison of freshly prepared and frozen cells from colorectal cancer surgical samples for phenotyping experiments- a pilot study
Presenter: Sandra Mersakova
Session: Poster Display session 3
Resources:
Abstract
3419 - Hyaluronan (HA) Accumulation in the Tumor Microenvironment (TME) is Increased in Colorectal Cancer (CRC) and Associated with Consensus Molecular Subtypes (CMS) 4 Molecular Subtype
Presenter: Barbara Blouw
Session: Poster Display session 3
Resources:
Abstract
1833 - Evaluation of CT-based radiomics in patients with renal cell carcinoma
Presenter: An Zhao
Session: Poster Display session 3
Resources:
Abstract
5883 - Detection of Double Protein Expression in Diffuse Large B Cell Lymphoma
Presenter: Mohamed Gouda
Session: Poster Display session 3
Resources:
Abstract
5415 - Encyclopedic Tumor Analysis for organ agnostic treatment with Axitinib in combination regimens for advanced cancers
Presenter: Tim Crook
Session: Poster Display session 3
Resources:
Abstract
3297 - Computational model to predict response rate of clinical trials
Presenter: Orsolya Lorincz
Session: Poster Display session 3
Resources:
Abstract
4355 - Analysis of BRCA genes and homologous recombination deficiency (HRD) scores in tumours from patients (pts) with metastatic breast cancer (mBC) in the OlympiAD trial
Presenter: Mark Robson
Session: Poster Display session 3
Resources:
Abstract