Pal SK, Bajorin D, Dizman N, et al. - Given the different biologic features of upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB), researchers investigated if infigratinib (BGJ398) [a potent and selective fibroblast grown factor receptor 1 to 3 (FGFR1‐3) inhibitor having significant activity in patients experiencing advanced or metastatic urothelial carcinoma bearing FGFR3 changes] showed varying activity in these settings. Cases with metastatic urothelial carcinoma with activating FGFR3 mutations and/or fusions were considered eligible. Infigratinib at a dose of 125 mg was administered to patients via oral route daily (3 weeks on/1 week off) until disease progression or intolerable toxicity. Eight patients with UTUC achieved 1 complete response [CR] and 3 partial responses [PRs] (overall response rate (ORR), 50%), and a best response of stable disease [SD](disease control rate (DCR), 100%) was noted in the rest of the patients. Experts reported 13 PRs in patients with UCB, and a best response of SD (DCR, 59.3%) in 22 patients. Higher frequencies of FGFR3‐TACC3 fusions and FGFR3 R248C mutations, and a lower frequency of FGFR3 S249C mutations, constituted the notable disparities in genomic changes between patients with UTUC and those with UCB. Overall, in the current FGFR3‐restricted experience, findings revealed disparities in the cumulative genomic profile between patients with UTUC and those with UCB, emphasizing the different biology of these diseases. A planned phase 3 adjuvant investigation mainly done in this population was supported by the findings.