Erdafitinib

A phase II trial included patients with metastatic urothelial carcinoma whose disease had progressed during or after systemic chemotherapy.[55] To be eligible for the study, patients were required to have tumors with an FGFR3 variant or an FGFR2::FGFR3 gene fusion. The trial was originally designed as a randomized phase II trial comparing continuous with intermittent treatment, but after an interim safety analysis, the trial was converted to a single-arm study of continuous treatment with dose escalation. The published analysis focuses on this latter phase of the study, referred to as the “selected-regimen group.” The selected-regimen group consisted of 99 patients, 74 with an FGFR3 variant and 25 with an FGFR2::FGFR3 gene fusion.

A phase II trial included patients with metastatic urothelial carcinoma whose disease had progressed during or after systemic chemotherapy.[55] To be eligible for the study, patients were required to have tumors with an FGFR3 variant or an FGFR2::FGFR3 gene fusion. The trial was originally designed as a randomized phase II trial comparing continuous with intermittent treatment, but after an interim safety analysis, the trial was converted to a single-arm study of continuous treatment with dose escalation. The published analysis focuses on this latter phase of the study, referred to as the “selected-regimen group.” The selected-regimen group consisted of 99 patients, 74 with an FGFR3 variant and 25 with an FGFR2::FGFR3 gene fusion.

The response rate by independent radiological review was 34%.

A phase II trial included patients with metastatic urothelial carcinoma whose disease had progressed during or after systemic chemotherapy.[55] To be eligible for the study, patients were required to have tumors with an FGFR3 variant or an FGFR2::FGFR3 gene fusion. The trial was originally designed as a randomized phase II trial comparing continuous with intermittent treatment, but after an interim safety analysis, the trial was converted to a single-arm study of continuous treatment with dose escalation. The published analysis focuses on this latter phase of the study, referred to as the “selected-regimen group.” The selected-regimen group consisted of 99 patients, 74 with an FGFR3 variant and 25 with an FGFR2::FGFR3 gene fusion.

The response rate was higher among the patients with FGFR3 variants than among the patients with FGFR2::FGFR3 gene fusions.

A phase II trial included patients with metastatic urothelial carcinoma whose disease had progressed during or after systemic chemotherapy.[55] To be eligible for the study, patients were required to have tumors with an FGFR3 variant or an FGFR2::FGFR3 gene fusion. The trial was originally designed as a randomized phase II trial comparing continuous with intermittent treatment, but after an interim safety analysis, the trial was converted to a single-arm study of continuous treatment with dose escalation. The published analysis focuses on this latter phase of the study, referred to as the “selected-regimen group.” The selected-regimen group consisted of 99 patients, 74 with an FGFR3 variant and 25 with an FGFR2::FGFR3 gene fusion.

Grade 3 adverse events that affected at least 10% of patients included stomatitis and hyponatremia. The most common adverse events of any grade were hypophosphatemia (77%), stomatitis (58%), diarrhea (51%), dry mouth (46%), decreased appetite (38%), and dysgeusia (37%).

A randomized controlled trial (THOR [NCT03390504]) included 266 patients with locally advanced or metastatic urothelial carcinoma who had received anti–PD-1 or anti–PD-L1 therapy. Patients had FGFR2 or FGFR3 pathogenic variants or gene fusions. The study compared erdafitinib with chemotherapy.[56][Level of evidence A1]

A randomized controlled trial (THOR [NCT03390504]) included 266 patients with locally advanced or metastatic urothelial carcinoma who had received anti–PD-1 or anti–PD-L1 therapy. Patients had FGFR2 or FGFR3 pathogenic variants or gene fusions. The study compared erdafitinib with chemotherapy.[56][Level of evidence A1]

At a median follow-up of 15.9 months, the OS was 12.1 months in the erdafitinib arm and 7.8 months in the chemotherapy arm (HR, 0.64; 95% CI, 0.47–0.88).

A randomized controlled trial (THOR [NCT03390504]) included 266 patients with locally advanced or metastatic urothelial carcinoma who had received anti–PD-1 or anti–PD-L1 therapy. Patients had FGFR2 or FGFR3 pathogenic variants or gene fusions. The study compared erdafitinib with chemotherapy.[56][Level of evidence A1]

The median PFS was 5.6 months in the erdafitinib arm and 2.7 months in the chemotherapy arm (HR, 0.58; 95% CI, 0.44–0.78).

A randomized controlled trial (THOR [NCT03390504]) included 266 patients with locally advanced or metastatic urothelial carcinoma who had received anti–PD-1 or anti–PD-L1 therapy. Patients had FGFR2 or FGFR3 pathogenic variants or gene fusions. The study compared erdafitinib with chemotherapy.[56][Level of evidence A1]

Grade 3 or higher treatment-related adverse events occurred in 45.9% of patients in the erdafitinib arm and 46.4% of patients in the chemotherapy arm. The most common grade 3 or higher events were hand-foot syndrome (9.6%), stomatitis (8.1%), onycholysis (5.9%), and hyperphosphatemia (5.2%) in the erdafitinib arm and neutropenia (14.3%) in the chemotherapy arm.

A randomized controlled trial (THOR [NCT03390504]) included 266 patients with locally advanced or metastatic urothelial carcinoma who had received anti–PD-1 or anti–PD-L1 therapy. Patients had FGFR2 or FGFR3 pathogenic variants or gene fusions. The study compared erdafitinib with chemotherapy.[56][Level of evidence A1]

Erdafitinib caused central serous retinopathy (CSR) of any grade in 17.0% of patients. CSR was grade 3 or higher in 2.2% of patients, which is consistent with prior safety data. Monthly ophthalmological examinations are recommended for the first 4 months of treatment and then every 3 months thereafter, as CSR may necessitate dose interruptions, dose reductions, and, sometimes, permanent erdafitinib discontinuation.