Response to immunotherapy, platinum-based chemotherapy or their combination in metastatic urothelial carcinoma (MUC) with or without FGFR-3 alterations: Single cohort experience.

Abstract

560 Background: Fibroblast growth factor receptor-3 (FGFR-3) is a promising target therapy in metastatic urothelial carcinoma. Its role in patient’s clinical outcome and treatment response is unclear. We present data for overall survival (OS) and response to platinum-based treatment, immunotherapy and combination (platinum plus immunotherapy) in MUC. Methods: Enrolled patients were diagnosed with muscle-invasive urothelial cancer (MIUC) between 2/2009-6/2019 at Clinic Hospital of Barcelona, Spain. All have been screened for FGFR-3 alterations using next-generation sequencing or qualitative real-time polymerase chain reaction-based assays in tumour or blood. Demographic, pathology, treatments and treatment response were collected retrospectively. Results: 101 patients with MIUC were screened, 99% had progressed to metastatic stage. At diagnosis 32.67% were metastatic. 77% were man and median age was 68y (38-85y). Median follow-up (FU) since metastatic disease was 16.25 months (1.2-89.72m) with 69.31% of patients had died at cut-off. 32% presented FGFR-3 alteration (fusion =1 and mutation=31). FGFR-3 altered more frequently had papillary histology than FGFR-3 wild type tumours (69 vs 26%, p<0.05). No statistical differences were detected between both groups for gender, age, stage at diagnosis, median FU, primary tumour site (upper vs lower tract) or previous history of non-invasive urothelial carcinoma. 58% patients received 1st line platinum-based chemotherapy, 25% immunotherapy and 8% the combination of both (9% with other therapies). FGFR-3 altered tended to present more benefit (complete, partial response or stable disease) with platinum-based chemotherapy than FGFR-3 wild type (81% vs 62%) but without reach statistical significance. No differences were detected for immunotherapy or combination therapies. Moreover, OS was similar for FGFR-3 altered (median 14.6m) and FGFR-3 wild- type (median 17.1 m) (HR 0.76, p=0.3). Conclusions: In our series, no significant differences related to response to first line therapy or survival was observed.