FGFR Inhibition Provides Significant Activity in Patients With UTUC, FGFR3 Alterations

Fibroblast growth factor receptor 3 (FGFR3) is the most common mutation in upper tract urothelial carcinoma (UTUC), found in 54% to 92% of diagnosed patients.

A recent phase 1b trial by Surena F. Matin, MD, and colleagues analyzed the effects of the FGFR inhibitor infigratinib in localized UTUC. Patients with localized UTUC have high unmet needs and tumors with a high frequency of FGFR3 alterations.

The trial enrolled 14 patients with localized UTUC who were undergoing ureteroscopy or nephroureterectomy/ureterectomy. Patients were administered infigratinib 125 mg orally every day for 21 days, then underwent 7 days without treatment before undergoing another 21-day treatment cycle.

The primary end point was tolerability monitored by Bayesian design and predefined stopping boundaries, and the secondary end point was objective response rate based on tumor mapping after endoscopic biopsy and post-trial surgery.

Patients were enrolled from May 2021 to November 2022, at which point the trial was closed due to the termination of all infigratinib oncology trials. Treatment-terminating toxicities occurred in only 2 (14.3%) patients.

Treatment response occurred in 6 (66.7%) of 9 patients with FGFR3 alterations. Responders had a median tumor size reduction of 67%, and 3 of 5 patients initially planned to undergo nephroureterectomy or ureterectomy were converted to ureteroscopy. The median follow-up in responders was 24.7 months (range, 14.9-28.9 months).

This first trial of targeted therapy for localized UTUC showed that FGFR inhibition is well tolerated and provides significant activity for patients with FGFR3-altered tumors. These results point to the feasibility of a biomarker-based phase 2 trial of FGFR inhibition in this patient population.