The following is a summary of “FORT-1: Phase II/III Study of Rogaratinib Versus Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Carcinoma Selected Based on FGFR1/3 mRNA Expression,” published in the January 2023 issue of Oncology by Sternberg, et al.

In patients with advanced urothelial carcinoma (UC) with FGFR1-3 mRNA overexpression, rogaratinib, an oral pan-fibroblast growth factor receptor (FGFR1-4) inhibitor, has shown encouraging phase I effectiveness and safety. For a study, researchers compared the effectiveness and safety of rogaratinib versus chemotherapy in patients with advanced/metastatic UC who had previously received platinum chemotherapy and tested positive for FGFR mRNA.

Phase II/III, randomized, open-label experiment FORT-1. Rogaratinib (800 mg orally twice daily, 3-week cycles; n = 87) or chemotherapy (docetaxel 75 mg/m2, paclitaxel 175 mg/m2, or vinflunine 320 mg/m2 intravenously once every 3 weeks; n = 88) were randomly assigned (1:1) to patients with FGFR1/3 mRNA-positive locally advanced or metastatic UC with ≥1 prior platinum-containing regimen. Overall survival was the main outcome, and an objective response rate (ORR) analysis was scheduled for after phase II enrollment. Enrollment was halted before phase III of the study was advanced due to the equivalent efficacy of the medications; a thorough interim analysis of phase II was done.

ORRs were 20.7% for rogaratinib (18/87; 95% CI: 12.7 to 30.7) and 19.3% for chemotherapy (17/88; 11.7 to 29.1). Overall median survival ranged between 8.3 and 9.8 months (95% CI, 6.5 to not estimable; hazard ratio, 1.11; 95% CI, 0.71 to 1.72; P =.67). Both 32 (39.0%)/15 (18.3%) and 37 (43.0%)/4 (4.7%) individuals experienced grade 3/4 incidents. There were no deaths brought on by rogaratinib. ORRs for rogaratinib were 52.4% (11/21; 95% CI, 29.8 to 74.3), and for chemotherapy 26.7% (4/15; 95% CI, 7.8 to 55.1). These results were from the exploratory investigation of patients with FGFR3 DNA mutations.

These were the first findings that showed comparable efficacy and tolerable safety when FGFR-directed treatment and chemotherapy are used in individuals with FGFR-altered UC. A preliminary analysis revealed that FGFR3 DNA changes in combination with FGFR1/3 mRNA overexpression may be more accurate indicators of rogaratinib response.