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Thomas Flaig, MD


Phase III Trial of Advanced Urinary Tract Cancers With FGFR Alterations: FGFR vs PD-L1 Inhibition

By: Celeste L. Dixon
Posted: Friday, November 17, 2023

Compared with the PD-L1 inhibitor pembrolizumab in one cohort of the phase III THOR trial, the FGFR inhibitor erdafitinib resulted in numerically longer progression-free survival and numerically higher overall response rates in pretreated patients with unresectable advanced or metastatic urothelial cancer who were anti–PD-L1 naive and had FGFR alterations, but no statistically significant difference in overall survival between the treatment arms. Arlene O. Siefker-Radtke, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues presented their work at the European Society for Medical Oncology (ESMO) Congress 2023 (Abstract 2359O).

FGFR-altered tumors are enriched in the luminal 1 subtype of urothelial cancer and, as such, may have only limited clinical benefit from anti–PD-L1 treatments such as pembrolizumab, the team noted. In contrast, erdafitinib is approved to treat locally advanced or metastatic urothelial cancer in patients with susceptible FGFR3/2 alterations whose disease has progressed after platinum-containing chemotherapy.

With a median follow-up of about 33 months, the intent-to-treat set included 175 adults in the erdafitinib arm (at 8 mg once daily, with pharmacodynamically guided uptitration to 9 mg) and 176 in the pembrolizumab arm (at 200 mg every 3 weeks). All study participants experienced disease progression after one prior treatment. Although toxicities were manageable with dose modifications, grade 3 or 4 treatment-related adverse effects and serious treatment-related adverse effects were reported in 43% and 13% of patients in the erdafitinib arm and in 12% and 10% of those in the pembrolizumab arm, respectively.

“The data from this new cohort provide early evidence suggesting there may be important impacts from the sequence of treatments for an FGFR3-altered urothelial cancer,” stated Dr. Siefker-Radtke in an MD Anderson press release. “Even though most primary FGFR-altered urothelial tumors are immunologically cold, it is possible that metastatic tumors may not share the same features. Perhaps these patients could benefit from combining erdafitinib with an immune checkpoint inhibitor.”

Disclosure: The study authors’ disclosure information can be found at

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