Erdafitinib is an oral pan-FGFR tyrosine kinase inhibitor approved to treat locally advanced/metastatic urothelial carcinoma (mUC) in patients with susceptible FGFR3/2 alterations (FGFRalt) who progressed after platinum-containing chemotherapy. FGFRalt tumours are enriched in luminal 1 subtype and may have limited clinical benefit from anti-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 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, FGFRalt 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.