Real world experience of FGFR gene alterations and clinical outcomes in advanced/metastatic urothelial cancer in Japan: MONSTAR-SCREEN database study.

Abstract

647 Background: Gene alterations (GA) in fibroblast growth factor receptors ( FGFR) may be oncogenic drivers in urothelial cancer (UC). However, the association between FGFR GA status and the prognosis with platinum-based chemotherapy has not been well investigated, especially in Asian patients. This study aims to elucidate the proportion and prognosis of FGFR2 or 3 (2/3) GA-positive advanced or metastatic UC (a/m UC). Methods: This study included patients registered during 2019 and 2022 in the “MONSTAR-SCREEN” database, where FoundationOneLiquid (F1L) was used for detecting 324 cancer-related genes, including FGFR. Analyzed FGFR2/3 GA variants included FGFR3 mutations (R248C, S249C, G370C, and Y373C) and FGFR2/3 fusions (FGFR2-BICC1, FGFR2-CASP7, FGFR3-TACC3, and FGFR3-BAIAP2L1). The positive ratio of FGFR2/3 GA and other gene alterations except FGFR was obtained at registration in eligible patients; besides, FGFR2/3 GA status was also evaluated after systemic treatment. Progression-free survival (PFS) in each treatment line was estimated, summarized by FGFR2/3 GA positive/negative. Results: Among the registered 2,224 cancer patients in this database, 138 eligible a/m UC patients were included (median age [SD] 72.0 [9.1] years for all; 95 males [68.8%]). The primary tumor site was the bladder in 70 patients (50.7%), renal pelvis in 50 patients (36.2%), and ureter in 18 patients (13.0%). FGFR2/3 GA was positive in 16 patients (11.6% [95% confidence interval: 6.8, 18.1]); the proportion of other typical gene alterations was 92.8%, 41.3%, 23.2%, and 23.2% in TP53, TERT, ARID1A and BRCA2, respectively. F1L was performed both before and after systemic treatment twice or more in 55 patients (39.9%). The FGFR concordance was analyzed in 55 patients available for both before and after treatment F1L results. Among them, 3 of the 6 FGFR2/3 GA-positive patients (50.0%) remained positive, and 1 of the 49 FGFR2/3 GA-negative patients (2.0%) before systemic treatment turned positive after treatment. The median PFS after first-line treatment was 6.8 months in FGFR GA-positive and 6.4 months in the negative patients. The estimated survival rate after first-line treatment was also similar between FGFR GA-positive and -negative patients at 12 months (68.8% vs. 81.0%). Conclusions: The results showed a similar trend to previous studies, where FGFR GA was reported in approximately 20% of metastatic UC patients. No difference was found in the PFS and the estimated survival rate by FGFR2/3 GA-positive or -negative patients. Our data showed that treatment pressure did not alter the FGFR status commonly.