Rogaratinib vs Chemotherapy in Previously Treated Patients With Advanced Urothelial Carcinoma and FGFR1/3 mRNA Overexpression

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As reported in the Journal of Clinical Oncology by Cora N. Sternberg, MD, and colleagues, interim analysis of the phase II portion of the phase II/III FORT-1 trial has shown similar objective response rates with the oral FGFR1–4 inhibitor rogaratinib vs chemotherapy in previously treated patients with advanced urothelial carcinoma and FGFR1/3 mRNA overexpression.

Due to the similar results in phase II evaluation, enrollment was stopped before progression to phase III evaluation.

Cora N. Sternberg, MD

Cora N. Sternberg, MD

Study Details

The open-label trial included 175 patients from sites in Asia, Europe, North America, and Australia with locally advanced or metastatic disease who were previously treated with at least one platinum-containing regimen. Patients were randomly assigned between May 2018 and March 2019 to receive rogaratinib at 800 mg twice daily (n = 87) or investigator’s choice of docetaxel at 75 mg/m2, paclitaxel at a175 mg/m2, or vinflunine at 320 mg/m2 every 3 weeks (n = 88). The primary endpoint was overall survival, with objective response rate analysis planned following phase II accrual.


Median follow-up was 10.8 months (95% confidence interval [CI] = 10.1–11.7 months). Objective response was observed in 18 patients (20.7%, 95% CI = 12.7%–30.7%) in the rogaratinib group vs 17 patients (19.3%, 95% CI = 11.7%–29.1%) in the chemotherapy group (rate difference = 1.4%, 95% CI = –10.5% to 13.2%, P = .48). Complete response was observed in two vs three patients. An additional 28% vs 35% of patients had stable disease. Median duration of response was 4.9 months (95% CI = 3.5–9.1 months) vs 5.8 months (95% CI = 3.5–7.7 months).

In an exploratory analysis among patients with FGFR3 DNA alterations in addition to FGFR1/3 mRNA overexpression, objective response was observed in 11 (52.4%, 95% CI = 29.8%–74.3%) of 21 patients in the rogaratinib group vs 4 (26.7%, 95% CI = 7.8%–55.1%) of 15 in the chemotherapy group.

Median progression-free survival was 2.7 months (95% CI = 1.6–4.6 months) in the rogaratinib group vs 3.2 months (95% CI = 2.7–4.4 months) in the chemotherapy group (HR = 1.23, P = .86).  Median overall survival was 8.3 months (95% CI = 6.5 months to not evaluable) with rogaratinib vs 9.8 months (95% CI = 6.8 months to not evaluable) with chemotherapy (HR = 1.11, P = .67).


  • No difference in objective response rate was observed for rogaratinib vs chemotherapy.
  • A higher response rate was observed with rogaratinib among patients with FGFR3 DNA alterations.

Adverse Events

Grade 3 adverse events occurred in 43.0% of patients in the rogaratinib group vs 39.0% of the chemotherapy group, with grade 4 events reported in 4.7% vs 18.3%. The most common grade 3 or 4 adverse events were asthenia (9.3%) and increased lipase (7.0%) in the rogaratinib group, and neutropenia (26.8%) and anemia (14.6%) in the chemotherapy group. Grade ≥ 2 retinal disorders occurred in 7.0% vs 0% of patients.

Adverse events led to discontinuation of treatment in 17.4% vs 11.0% of patients. No deaths related to rogaratinib were reported.  

The investigators concluded, “To our knowledge, these are the first data to compare FGFR-directed therapy with chemotherapy in patients with FGFR-altered urothelial carcinoma, showing comparable efficacy and manageable safety. Exploratory testing suggested FGFR3 DNA alterations in association with FGFR1/3 mRNA overexpression may be better predictors of rogaratinib response.”

David I. Quinn, MBBS, PhD, of the Division of Oncology, USC Norris Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by Bayer AG. For full disclosures of the study authors, visit

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