Clinicopathological characterization, FGFR alteration prevalence, and outcomes of locally advanced or metastatic urothelial cancer in Latin America (LACOG 1518).

Abstract

e16549 Background: Treatment of Urothelial Cancer (UC) is rapidly evolving with innovative biomarker-based approaches. Alterations in the gene encoding fibroblast growth factor receptor (FGFR) are frequent in UC and are an emerging focus for targeted therapy. However, real-world data on FGFR prevalence, as well as clinicopathological characteristics and outcomes of patients (pts) with advanced UC in Latin America is lacking. Methods: LACOG 1518 is a multicenter multinational study that retrospectively included pts diagnosed with metastatic or relapsed UC between Jan-2016 and Dec-2019. Clinicopathological characteristics, outcomes and treatment patterns were retrieved from medical records. Archival tumor samples were analyzed for FGFR alterations by NGS. Results: Two hundred thirteen pts were included across 24 centers in 4 Latin American countries. Median age was 68 years (range, 31-90), most pts (75%) had PS 0-1, and 83 (39%) pts had clinical stage IV at diagnosis. Bladder was the primary site of disease in 190 (89%) pts, 92 (43.2%) pts had histological variants of UC - 46 (21.6%) pts with adenocarcinoma differentiation and 16 (7.5%) with squamous-cell differentiation. Patients with relapsed locoregional disease not candidates for curative therapy comprised 10.3% of the sample. Among pts with metastatic disease, visceral metastases were present in 99 (51%) pts. FGFR alterations eligible for treatment with FGFR inhibitors (FGFRi) were identified in 29 (14.8%) out of 196 pts tested and included 29 mutations (14 S249C, 7 Y373C, 5 R248C and 3 G370C) and 13 fusions (8 FGFR3-TACC3, 2 FGFR3-BAIAP2L1, 2 FGFR2-BICC1 and 1 FGFR2-CASP7). Other FGFR alterations were also present in 6 (3.1%) pts. Median overall survival since initial diagnosis and advanced disease were 31.6 months (95% CI, 25.5 – 37.6) and 15.2 months (95% CI, 12.4 – 17.9), respectively. Median time to treatment failure to the first treatment line was 3.9 months (95% CI, 3.0 – 4.4). Regarding treatment patterns, 175 (82.1%) pts received first line treatment: 127 (72.6%) combined chemotherapy, 29 (16.6%) immunotherapy alone, 15 (8.6%) single agent chemotherapy, and 4 (2.3%) chemo-immunotherapy. Gemcitabine-platinum combinations were the backbone of choice in 93.7% of pts receiving combined chemotherapy. Pembrolizumab and atezolizumab were the chosen first-line agents for 10.3% and 4% of the treated pts, respectively. Considering all treatment lines, 75 (35.2%) and 3 (1.4%) pts were exposed to immunotherapy and FGFRi in the course of their disease, respectively. Conclusions: The prevalence of FGFR alterations in advanced UC in Latin America is similar to those described in other regions. Our data suggest limited access to FGFR inhibitors for the treatment of advanced UC in Latin America.