Targeted agent rogaratinib noninferior to chemo in FGFR+ advanced urothelial carcinoma


Findings from the phase 2/3 FORT-1 study (NCT03410693) showed comparable efficacy and safety with the targeted agent rogaratinib vs chemotherapy in patients with FGFR1/3 mRNA–positive advanced urothelial carcinoma previously treated with platinum chemotherapy.1

The objective response rate (ORR) was 20.7% (n = 18/87; 95% CI, 12.7%-30.7%) for patients receiving rogaratinib vs 19.3% (n = 17/88; 95% CI, 11.7%-29.1%) for those receiving chemotherapy. The median overall survival (OS) was 8.3 months (95% CI, 6.5-not estimable [NE]) for the rogaratinib cohort compared with 9.8 months (95% CI, 6.8-NE) for patients in the chemotherapy arm (HR, 1.11; 95% CI, 0.71-1.72; = .67).

The randomized, open-label phase 2 FORT-1 trial was designed to assess the efficacy and safety of FGFR-inhibitor rogaratinib vs standard chemotherapy in a population of 175 patients with advanced or metastatic urothelial carcinoma harboring an overexpression of FGFR1 or FGFR3 who received prior platinum chemotherapy. Investigators randomly assigned patients 1:1 to either receive 800 mg of oral rogaratinib taken twice a day in 3-week continuous cycles (n = 87) or chemotherapy that could include 75 m/m2 of docetaxel, 175 mg/m2 of paclitaxel, or 320 mg/m2 of vinflunine administered intravenously once every 3 weeks (n = 88). Patients continued treatment until disease progression, unacceptable toxicity, or trial withdrawal.

The primary end point for this trial was OS. Secondary end points included progression-free survival, ORR, disease control rate (DCR), duration of response, and safety and tolerability.

Patients 18 years and older with histologically or cytologically confirmed advanced or metastatic urothelial carcinoma were eligible to enroll on the trial. Patients were also required to have an ECOG performance status of 0 or 1 and have an archival or fresh tissue biopsy.

The median patients age was 69 years (range, 36-89) in the overall treatment population. Most patients were from North America, Western Europe, Israel, or Australia (67.4%). Most patients had primary cancer of the bladder (57.7%), an absence of liver metastases (66.3%), stage IV B disease at study entry (65.7%), an absence of PIK3CA-/RAS-activating mutations (71.4%), and a low risk modified 4-factor Bellmunt score (82.3%). Additionally, less than half of enrolled patients received prior immunotherapy (44.6%).

Findings from a retrospective, exploratory analysis indicated that the ORR among patients with FGFR3 DNA alterations who were treated with rogaratinib was 52.4% (95% CI, 29.8%-74.3%) and 11.5% (95% CI, 4.7%-22.2%) among those who were FGFR3 wild-type compared with 26.7% (95% CI, 7.8%-55.1%) and 17.2%, respectively for those in the chemotherapy arm. Additionally, DCR for patients with FGFR3 DNA alterations was 76.2% (95% CI, 52.8%-91.8%) and 45.9% (95% CI, 33.1%-59.2%) among those with wild-type disease who were treated with rogaratinib and 66.7% (95% CI, 38.4-88.2) and 51.6% (95% CI, 38.7%-64.2%), respectively, for those receiving chemotherapy.

Grade 3 treatment-emergent adverse effects (TEAEs) were seen in 43.0% of patients receiving rogaratinib and 39.0% of those receiving chemotherapy. Grade 4 TEAEs occurred in 4.7% and 18.3% of patients, respectively. Gastrointestinal toxicities were among the most observed any-grade TEAES for those receiving rogaratinib vs the chemotherapy arm, which included diarrhea (55.8% vs 23.2%), nausea (32.6% vs 23.2%), and constipation (29.1% vs 35.4%). Hyperphosphatemia was also another common TEAE observed in the rogaratinib population, occurring in 45.3% of patients compared with 0.0% in the comparator arm.

Grade 5 TEAEs occurred in 11.3% of patients in the overall study, including 16.3% of those in the experimental arm and 6.1% of those in the chemotherapy arm. Common grade 5 AEs in the experimental arm were physical health deterioration (n = 3) and dyspnea (n = 3), neither of which were related to treatment. One event of grade 5 respiratory tract infection in the chemotherapy arm was determined to be related to treatment.


1. Sternberg CN, Petrylak DP, Bellmunt J, et al. 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. J Clin Oncol. Published online October 14, 2022. doi:10.1200/JCO.21.02303

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