Erdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor approved to treat locally advanced/metastatic urothelial carcinoma (mUC) in patients with susceptible FGFR3/2 alterations (FGFR alt) who progressed after platinum-containing chemotherapy. FGFR -altered tumours are enriched in luminal 1 subtype and may have limited clinical benefit from anti–programmed death-(ligand) 1 [PD-(L)1] treatment. This cohort in the randomized, open-label phase III THOR study assessed erdafitinib versus pembrolizumab in anti–PD-(L)1-naive patients with mUC. Patients ≥18 years with unresectable advanced/mUC, with select FGFRalt , disease progression on one prior treatment, and who were anti–PD-(L)1-naive were randomized 1 : 1 to receive erdafitinib 8 mg once daily with pharmacodynamically guided uptitration to 9 mg or pembrolizumab 200 mg every 3 weeks. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. The intent-to-treat population (median follow-up 33 months) comprised 175 and 176 patients in the erdafitinib and pembrolizumab arms, respectively. There was no statistically significant difference in OS between erdafitinib and pembrolizumab [median 10.9 versus 11.1 months, respectively; hazard ratio (HR) 1.18; 95% confidence interval (CI) 0.92-1.51; P = 0.18]. Median PFS for erdafitinib and pembrolizumab was 4.4 and 2.7 months, respectively (HR 0.88; 95% CI 0.70-1.10). ORR was 40.0% and 21.6% (relative risk 1.85; 95% CI 1.32-2.59) and median duration of response was 4.3 and 14.4 months for erdafitinib and pembrolizumab, respectively. 64.7% and 50.9% of patients in the erdafitinib and pembrolizumab arms had ≥1 grade 3-4 adverse events (AEs); 5 (2.9%) and 12 (6.9%) patients, respectively, had AEs that led to death. Erdafitinib and pembrolizumab had similar median OS in this anti–PD-(L)1-naive, FGFR -altered mUC population. Outcomes with pembrolizumab were better than assumed and aligned with previous reports in non– FGFR -altered populations. Safety results were consistent with the known profiles for erdafitinib and pembrolizumab in this patient population. • Erdafitinib was not superior to pembrolizumab with similar efficacy outcomes in FGFR -altered, anti -PD-(L)1-naive mUC. • The primary endpoint was not met; median OS was 10.9 months for erdafitinib and 11.1 months for pembrolizumab. • Outcomes with pembrolizumab in mUC with FGFR alterations were similar to those reported for FGFR -unselected populations. • Safety was consistent with known safety profiles for erdafitinib and pembrolizumab; erdafitinib toxicities were manageable. [ABSTRACT FROM AUTHOR]