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JU INSIGHT Targeted Fibroblast Growth Factor Receptor Inhibition in Localized Upper Tract Urothelial Carcinoma

By: Surena F. Matin, MD, MD Anderson Cancer Center, Houston, Texas; Mehrad Adibi, MD, MD Anderson Cancer Center, Houston, Texas; Amishi Y. Shah, MD, MD Anderson Cancer Center, Houston, Texas; Omar Alhalabi, MD, MD Anderson Cancer Center, Houston, Texas; Paul Corn, MD, MD Anderson Cancer Center, Houston, Texas; Charles Guo, MD, MD Anderson Cancer Center, Houston, Texas; Rhenita Amirtharaj, RN, MD Anderson Cancer Center, Houston, Texas; Lianchun Xiao, PhD, MD Anderson Cancer Center, Houston, Texas; Suzanne Lange, MD, MD Anderson Cancer Center, Houston, Texas; Dzifa Y. Duose, PhD, MD Anderson Cancer Center, Houston, Texas; Shufang Wang, PhD, MD Anderson Cancer Center, Houston, Texas; Sumanta Pal, MD, City of Hope, Duarte, California; Matthew T. Campbell, MD, MD Anderson Cancer Center, Houston, Texas | Posted on: 18 Jun 2024

Matin SF, Adibi M, Shah AY, et al. Phase 1b trial evaluating tolerability and activity of targeted fibroblast growth factor receptor inhibition in localized upper tract urothelial carcinoma. J Urol. 2024;211(6):784-793. doi:10.1097/JU.0000000000003928

Study Need and Importance

Treatment of localized upper tract urothelial carcinoma (UTUC) suffers from significant unmet needs, including limited options for organ preservation. With recent data confirming high rates of FGFR (fibroblast growth factor receptor) 3 mutations in UTUC, we designed a preoperative biomarker-informed study in patients with localized UTUC to further understand tolerability and biologic consequences of FGFR inhibition, previously unstudied in the localized setting.

What We Found

Over 18 months, 14 patients were enrolled, 2 of whom had toxicities preventing the full duration of treatment, well below the predetermined stopping threshold. There were no delays to surgery. Most adverse events were low grade and reversible. Nine (64.3%) of 14 patients were found to have FGFR3 alterations. Responses were seen in 6 (66.7%) of the 9 patients with FGFR3 alterations, including 2 with high-grade disease, demonstrating 67% (range 25%-88%) median tumor size reduction in the 6 responders, 5 of whom were initially planned to undergo nephroureterectomy, of which 3 were converted to endoscopic management (Figure). No responses were seen in the 5 without FGFR3 alterations. During a median follow-up of 24.7 months, no patients experienced distant metastases or died.

IMAGE

Figure. Waterfall plot showing tumor size responses based on fibroblast growth factor receptor (FGFR) status, high-grade tumors, and cases converted from initial planned nephroureterectomy to successful organ preservation.

Limitations

Early termination of the trial limited the ability to obtain additional response data. Despite these limitations and early termination, the study met tolerability criteria and provided strong efficacy data for further exploration in those with FGFR3-altered tumors.

Interpretation for Patient Care

This first trial of short-duration targeted therapy supports the design of a phase 2 trial of FGFR inhibition in patients with FGFR3-altered UTUC, with the aim of converting them to organ preservation and de-escalated surgical interventions.

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