Optimal Rogaratinib Dose for Cisplatin-Ineligible Patients With FGFR RNA-Overexpressing Advanced Urothelial Cancer
According to results from the phase 1b FORT-2 study, the addition of 600 mg of rogaratinib, a selective pan-FGFR inhibitor, is preferable to 800 mg among cisplatin-ineligible patients with FGFR RNA-overexpressing locally advanced or metastatic urothelial cancer being treated with atezolizumab.
In this multicenter, open-label, single-arm study, researchers enrolled 37 previously untreated patients to receive either 600 mg (n = 26) or 800 mg (n = 11) of twice daily rogartinib plus 1200 mg of atezolizumab every 21 days until disease progression or unacceptable toxicity. Primary end points included safety and tolerability. Key secondary efficacy end points included median progression-free survival (PFS) and median overall survival (OS).
At analysis, median treatment duration was 4.1 months in the 600 mg arm and 1.4 months in the 800 mg arm. The most common treatment-related adverse events included diarrhea (62%) and hyperphosphatemia (51%). Adverse events led to treatment discontinuation in 27% of patients in the 600 mg arm and 55% of patients in the 800 mg arm. The most common grade ≥ 3 treatment-related serious adverse events included increased alanine aminotransferase, increased aspartate aminotransferase, asthenia, dehydration, hemorrhagic diarrhea, and abnormal kidney function test.
The median PFS was 7.5 months in the 600 mg arm and 2.1 months in the 800 mg arm and the median OS was 16.8 months and 8.3 months, respectively.
Efficacy “was observed in tumors with low PD-L1 and was not dependent on FGFR3 gene alterations, suggesting broad potential benefit for patients with locally advanced/metastatic [urothelial cancer] and FGFR mRNA overexpression,” concluded Dr Sweis et al.
Source:
Sweis RF, Gajate P, Morales-Barrera R, et al. Rogaratinib plus atezolizumab in cisplatin-ineligible patients With FGFR RNA-overexpressing urothelial cancer. JAMA Oncol. Published online: September 19, 2024. doi:10.1001/jamaoncol.2024.3900
