Dr. Iyer on Investigational FGFR Inhibitors in Metastatic Urothelial Carcinoma

Gopa Iyer, MD
Published: Friday, Mar 20, 2020



Gopa Iyer, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses investigational FGFR inhibitors in metastatic urothelial carcinoma.

In a phase I study, the pan-FGFR kinase inhibitor infigratinib demonstrated an overall response rate of 25.4% in patients with advanced or metastatic urothelial carcinoma with FGFR3 activating mutations or fusions and prior platinum-based chemotherapy. Currently, the agent is being tested in the phase III PROOF 302 trial as adjuvant therapy in high-risk patients with invasive urothelial carcinoma and susceptible FGFR3 genetic alterations.

Rogaratinib is another agent under investigation for patients with metastatic disease. However, the agent is being evaluated in patients with FGFR3 overexpression, as detected with an RNA-based assay, rather than FGFR3 mutations or fusions, says Iyer.

Currently, rogaratinib is being compared with chemotherapy in the phase II/III FORT-1 study in patients with FGFR-positive locally advanced or metastatic urothelial carcinoma who have received prior platinum-containing chemotherapy. Additionally, the agent is being studied in combination with atezolizumab (Tecentriq) in the phase Ib/II FORT-2 trial as first-line treatment for cisplatin-ineligible patients with FGFR-positive locally advanced or metastatic urothelial carcinoma.

Finally, pemigatinib is being evaluated as a single-agent and in combination with pembrolizumab (Keytruda) in the phase II FIGHT-205 study. Patients must have newly diagnosed, metastatic or unresectable urothelial carcinoma and harbor an FGFR3 mutation or rearrangement to be eligible for enrollment. Another FGFR inhibitor from AstraZeneca that will be looked at alone and in combination with durvalumab (Imfinzi) is in development, Iyer concludes.
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Gopa Iyer, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses investigational FGFR inhibitors in metastatic urothelial carcinoma.

In a phase I study, the pan-FGFR kinase inhibitor infigratinib demonstrated an overall response rate of 25.4% in patients with advanced or metastatic urothelial carcinoma with FGFR3 activating mutations or fusions and prior platinum-based chemotherapy. Currently, the agent is being tested in the phase III PROOF 302 trial as adjuvant therapy in high-risk patients with invasive urothelial carcinoma and susceptible FGFR3 genetic alterations.

Rogaratinib is another agent under investigation for patients with metastatic disease. However, the agent is being evaluated in patients with FGFR3 overexpression, as detected with an RNA-based assay, rather than FGFR3 mutations or fusions, says Iyer.

Currently, rogaratinib is being compared with chemotherapy in the phase II/III FORT-1 study in patients with FGFR-positive locally advanced or metastatic urothelial carcinoma who have received prior platinum-containing chemotherapy. Additionally, the agent is being studied in combination with atezolizumab (Tecentriq) in the phase Ib/II FORT-2 trial as first-line treatment for cisplatin-ineligible patients with FGFR-positive locally advanced or metastatic urothelial carcinoma.

Finally, pemigatinib is being evaluated as a single-agent and in combination with pembrolizumab (Keytruda) in the phase II FIGHT-205 study. Patients must have newly diagnosed, metastatic or unresectable urothelial carcinoma and harbor an FGFR3 mutation or rearrangement to be eligible for enrollment. Another FGFR inhibitor from AstraZeneca that will be looked at alone and in combination with durvalumab (Imfinzi) is in development, Iyer concludes.



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