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Thomas Flaig, MD


Early-Phase Study of Infigratinib Supports Further Work in Metastatic Urothelial Carcinoma

By: Celeste L. Dixon
Posted: Monday, March 21, 2022

The results of a 67-patient phase Ib study indicate that infigratinib may have activity in metastatic urothelial cancer regardless of what line of therapy it is given in. According to Petros Grivas, MD, PhD, of Fred Hutchinson Cancer Research Center in Seattle, and colleagues, infigratinib—a selective FGFR1-3 tyrosine kinase inhibitor—now deserves evaluation not only across different lines of therapy, but across different treatment settings in metastatic urothelial cancer. And, they reported in Clinical Genitourinary Cancer, infigratinib is currently being explored in a placebo-controlled, double-blind, randomized phase III adjuvant trial (PROOF 302; Clinical identifier NCT04197986).

In this single-arm, open-label trial, eligible patients had metastatic urothelial cancer and prior platinum-based chemotherapy, unless contraindicated, and an activating FGFR3 mutation/fusion. The primary endpoint was investigator-assessed confirmed objective response rate, and it was met. This rate, overall, was 25.4%: 30.8% in the 13 patients who received infigratinib as early-line therapy (because of their ineligibility to receive platinum-based chemotherapy) and 24.1% in the remainder of the cohort, who received it as a second- or later-line therapy. No significant differences in toxicities emerged based on the line of therapy. All patients received infigratinib at 125 mg daily, by mouth, 3 weeks on and 1 week off.

The researchers made special mention that infigratinib had significant activity in the eight-patient subset who had upper urinary tract primary tumors, a tumor type enriched for FGFR3-driven biology. Also notable, they wrote, was that “the rate of hyperphosphatemia, an ‘on-target’ mechanism-based toxicity correlated with treatment efficacy,” was similar in both the early-line and salvage settings (38.9% vs. 38.5%).

All of these results should “inform discussions about therapy sequencing,” noted Dr. Grivas and co-investigators. “The availability of expanded treatment options has led to questions about how to optimally sequence and/or combine these therapies, and whether patients with FGFR2 or FGFR3 alterations should receive an FGFR inhibitor earlier in the course of their disease.”

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

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