Dr Petrylak on the Potential Use of Erdafitinib in Metastatic Urothelial Cancer

Daniel P. Petrylak, MD, professor, medicine, Medical Oncology and Urology, chief, Genitourinary Oncology, Yale School of Medicine, discusses the potential uses forerdafitinib (Balversa), highlighting key studies evaluating the use of the agent in patients with metastatic urothelial cancer.

Urothelial cancer can develop resistance to FGFR3 inhibitors through multiple pathways, which are referred to as gatekeeper mutations, Petrylak begins. For example, resistance can happen when alternate pathways, such as MET, are upregulated, he says. This happens when the binding pockets to FGFR3 inhibitors are modified, thereby preventing drug binding. MAP kinase, PI3K, JAK-STAT, and GSK3B are all additional intracellular signaling pathways that are activated, Petrylak notes, adding that epithelial-to-mesenchymal transition can also occur.

Looking at initial data in the FGFR3-targeted clinical space, the phase 2 BLC2001 clinical trial (NCT02365597) evaluated the efficacy and safety of erdafitinib in patients with urothelial cancer. In this study, patients with locally advanced and unresectable or metastatic urothelial carcinoma with FGFR alterations had an objective response rate (ORR) of 40% (95% CI, 31%-50%). Notably, en vitro studies have demonstrated that treatment with erdafitinib can lead to tumor infiltration of CD4-and CD8-positive T cells, Petrylak expands.

Furthermore, data from the phase 2 NORSE study (NCT03473743) of erdafitinib in patients with metastatic or locally advanced urothelial cancer were presented at the 2023 ASCO Annual Meeting, showing a potential trend toward a better ORR with erdafitinib and the checkpoint inhibitor cetrelimab (JNJ-63723283) vs erdafitinib alone, he continues. This combination creates the potential for oncologists to convert a cold tumor to a hot tumor by treating a patient with an FGFR inhibitor, Petrylak explains. There are various treatment routes being evaluated with the use of FGFR3 inhibitors, including ongoing investigations at the Yale School of Medicine, Petrylak concludes, saying that investigations into this pathway will be expanding.