Abstract 758P
Background
Limited data are available on the prognostic and predictive value of FGFRa in pts with high-risk NMIBC. We assessed the role of FGFRa in a real-world cohort comprising solely pts with stage pT1 high-risk NMIBC and the effect of bacillus Calmette-Guérin (BCG) therapy.
Methods
We assessed a pooled dataset of matched clinical and genomic data for pts with stage pT1 NMIBC treated (1992-2015) by the Bladder Cancer Research Initiative for Drug Targets in Germany (BRIDGE) consortium. FGFRa status was defined by prespecified panel of FGFR2/3 mutations and fusions via QIAGEN therascreen® FGFR test. FGFR1-4 mRNA expression was assessed by single-step RT-qPCR. Recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS) were estimated by Kaplan-Meier analysis. Hazard ratio (HR) was calculated by multivariate Cox proportional hazards model.
Results
Of 263 analyzed pts, 43% had FGFRa (39% mutations, 6% fusions, not mutually exclusive), 27% had concomitant carcinoma in situ (CIS), and 42% received BCG. Spearman correlation showed significant inverse associations between FGFR3a mRNA levels and WHO 1973 grade (ρ -0.3220, p < 0.0001) and CIS (ρ -0.2101, p < 0.0006). FGFR3 mRNA levels positively correlated with FGFR3a (ρ 0.6115, p < 0.0001). Presence of FGFRa was not associated with RFS, PFS, or DSS overall or when stratified by BCG-treated or BCG-naïve pts (Table). Stage pT1 pts with or without FGFRa had similar survival outcomes in response to BCG. Table: 758P
| Pts with FGFRa vs pts without FGFRa | RFS HR (95% CI) p Value | PFS HR (95% CI) p Value | DSS HR (95% CI) p Value |
| Overall cohort | 0.93 (0.60-1.43) | 0.60 (0.31-1.16) | 0.59 (0.29-1.23) |
| 0.724 | 0.121 | 0.154 | |
| Pts with BCG treatment | 0.66 (0.32-1.36) | 0.32 (0.09-1.15) | 0.39 (0.08-1.87) |
| 0.251 | 0.066 | 0.221 | |
| Pts without treatment | 0.83 (0.44-1.57) | 0.68 (0.28-1.62) | 0.68 (0.28-1.64) |
| 0.558 | 0.374 | 0.387 |
Conclusions
FGFRa were frequent in high-risk pts. In stage pT1 NMIBC, distinct from previous reports, prognosis for pts with FGFRa was not different from those without FGFRa. Pts with FGFRa who had recurrence/relapse post-BCG treatment have high unmet need. The role of FGFR directed therapy is being investigated in a randomized study (NCT03390504).
Clinical trial identification
Editorial acknowledgement
Sally Hassan PhD, CMPP, of Parexel International provided editorial assistance for this abstract.
Legal entity responsible for the study
Janssen Research & Development, LLC.
Funding
Janssen Research & Development, LLC.
Disclosure
J. Breyer: Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Research grant/Funding (institution): Cepheid; Honoraria (self): Ipsen; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (institution): Bristol Myers Squibb, AstraZeneca, Merck; Honoraria (self): Roche. M. Monga: Full/Part-time employment: Janssen. R. Mayr: Travel/Accommodation/Expenses: Ipsen. M. Burger: Honoraria (self), Speaker Bureau/Expert testimony: Bristol Myers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen. M. Eckstein: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Full/Part-time employment: Diaceutics; Honoraria (self), Speaker Bureau/Expert testimony: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen-Cilag; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Astellas; Advisory/Consultancy, Travel/Accommodation/Expenses: GenomicHealth. R. Stöhr: Full/Part-time employment: Universitiy Hospital Erlangen, Germany Institute of Pathology. P. Erben: Research grant/Funding (self): Janssen. C. Bolenz: Honoraria (self), Research grant/Funding (institution): Janssen; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: Takeda; Research grant/Funding (institution): ERBE. S. Eidt: Leadership role, Shareholder/Stockholder/Stock options: Stratifyer, Molecula Pathology. R. Sundaram: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: Johnson & Johnson. M. Baig: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: Johnson & Johnson. A. Galluzzi: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: Johnson & Johnson. R. Wirtz: Leadership role, Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Licensing/Royalties, Officer/Board of Directors: Stratifyer; Advisory/Consultancy, Research grant/Funding (institution): Janssen, Johnson & Johnson; Advisory/Consultancy, Research grant/Funding (institution), Licensing/Royalties: BioNTech; Advisory/Consultancy, Travel/Accommodation/Expenses: Medicover; Research grant/Funding (self), Licensing/Royalties: Qiagen; Advisory/Consultancy, Research grant/Funding (institution): Intellexon. A. Hartmann: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Janssen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Honoraria (institution), Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Cepheid. A. Santiago-Walker: Shareholder/Stockholder/Stock options, Full/Part-time employment: Janssen. All other authors have declared no conflicts of interest.