2398P - Are fibroblast growth factor receptor 3 (FGFR3) alterations a possible predictive factor for platinum-based chemotherapy and immunotherapy in metastatic urothelial carcinoma (MUC)?

Background

FGFR3 is associated to proliferation, differentiation and cellular growth. FGFR3 alterations are present in 25% of patients (pts) with MUC and FGFR3 inhibition is an active targeted therapy. However, the role of FGFR3 alterations in patients’ clinical outcomes and response to conventional treatment is unclear and no pre-clinical evidence is available.

Methods

Unicenter retrospective study was performed to explore the correlation between FGFR3 alterations and response rate (ORR), progression free survival (PFS) and overall survival (OS) to platinum-based therapies or immunotherapy. Enrolled pts were diagnosed with muscle-invasive urothelial cancer (MIUC) between 2/2009- 3/2022 at Clinic Hospital of Barcelona, Spain. All were screened for FGFR-3 alterations using next-generation sequencing, qualitative real-time polymerase chain reaction-based assays or RNA-ISH in tumour and/or blood. Demographics, pathology, treatments outcomes were collected retrospectively.

Results

189 pts with MIUC were included: 74.6% were men, median age was 68.5 (37.6-89.7y). Clinical stage at diagnosis was: 10% II, 44% III, 46% IV. Median follow-up since metastatic disease diagnosis was 16.2 months (0.3-91m). 77% of pts had died at data cut-off. 25.4% had FGFR3 alterations (mutation= 36; fusion= 6; double alteration= 3; RNA-ISH amplification =3). FGFR3 altered (FGFR3-alt) tumours were enriched with papillary histology compared with FGFR3 wild type (FGFR3-wt) (33 vs 11%, p<0.05). No statistical differences were detected in other baseline characteristics. 66.5% (N=113) pts received 1^st-line platinum-based chemotherapy (1^st PT) and 58% (N=69) 2^nd-line immunotherapy (2^nd IO). No statistically significant differences were detected in OS (15.2 vs 17.5m), PFS (5.6 vs 7.2m), ORR (62 vs 55%) for pts treated with 1^st PT according to FGFR3-alt or FGFR3-wt. In 2^nd IO, FGFR3-alt had less ORR than FGFR3-wt (9 vs 41%)(p=0.32) and no statistically significant differences in OS (9.7 vs 12.1m) or PFS (3 vs 3.9m) were observed.

Conclusions

In our cohort, FGFR3 alterations are neither predictive nor prognostic for 1st-line platinum or 2nd-line IO. Further investigation is needed.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

L. Ferrer-Mileo: Financial Interests, Personal, Other, speaker, travel accommodation: Pfizer; Financial Interests, Personal, Invited Speaker, speaker, travel accommodation: Kyowa Kirin; Financial Interests, Personal, Invited Speaker, Speaker: Ipsen, Janssen. C. Aversa: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Janssen, BMS; Other, Travel funding: Janssen. B. Mellado Gonzalez: Financial Interests, Personal, Other, Research Grant/Funding (Self), Speaker Bureau, Travel accommodation: Jansen, Roche, Astellas, Sanofi, Bayeri; Financial Interests, Personal, Other, Speaker Bureau, Travel accommodation: Pfizer; Financial Interests, Personal, Other, Travel accommodation, Speaker Bureau: Ipsen; Financial Interests, Personal, Other, Speaker Bureau: BMS. O. Reig Torras: Financial Interests, Personal, Invited Speaker: Pfizer, BMS, Ipsen. All other authors have declared no conflicts of interest.