The European Commission (EC) has given the green light for the use of Balversa (erdafitinib) as an oral, once-daily monotherapy to treat adult patients with unresectable or metastatic urothelial carcinoma (mUC) who harbor susceptible FGFR3 genetic alterations and have previously undergone at least one line of therapy involving a PD-1 or PD-L1 inhibitor.
First Pan-FGFR Inhibitor Approved in European Economic Area
BALVERSA, the first pan-FGFR kinase inhibitor to be approved within the European Economic Area, offers a new treatment option for patients with advanced or metastatic urothelial carcinoma. The approval was largely based on data from the Phase 3 THOR study, which revealed a 36% reduction in the risk of death for patients treated with erdafitinib compared to those receiving chemotherapy.
Study Findings and Outcomes
The approval of erdafitinib was supported by findings from the THOR study's Cohort 1, which assessed the drug's efficacy and safety in patients with advanced mUC who have specific FGFR genetic alterations. The trial included patients who had progressed after one or two prior treatments, with at least one being a PD-1 or PD-L1 inhibitor. The study was stopped early in June 2023 following an interim analysis, which showed significant efficacy. Patients initially assigned to chemotherapy were given the option to switch to erdafitinib.
The study results indicated a median overall survival (OS) of over one year for patients treated with erdafitinib, compared to 7.8 months for those on chemotherapy. Additionally, patients receiving erdafitinib experienced a median progression-free survival (PFS) of 5.6 months, compared to 2.7 months in the chemotherapy group. The overall response rate (ORR) was also higher with erdafitinib (35.3%) compared to chemotherapy (8.5%).
Safety Profile and Adverse Events
Serious treatment-related adverse events (TRAEs) were observed in 13.3% of patients treated with erdafitinib, while 24.1% of those in the chemotherapy group experienced serious TRAEs. Grade 3 or higher adverse events occurred in 45.9% of patients receiving erdafitinib and 46.4% of those on chemotherapy. A smaller percentage of patients on erdafitinib discontinued treatment due to TRAEs (8.1%) compared to the chemotherapy group (13.4%). There was one reported TRAE-related death among the erdafitinib group, while six deaths were reported in the chemotherapy group.
About the THOR Study
The THOR study was a Phase 3, randomized, open-label, multicenter trial that evaluated erdafitinib’s efficacy and safety in patients with metastatic or unresectable urothelial carcinoma and specific FGFR genetic alterations. Patients were randomized into two cohorts: one comparing erdafitinib to standard chemotherapy after at least one line of treatment, including a PD-1 or PD-L1 inhibitor, and the other comparing erdafitinib to pembrolizumab following a prior treatment not containing a PD-1 or PD-L1 inhibitor.
The primary endpoint of the study was overall survival (OS), with secondary endpoints including progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), patient-reported outcomes, safety, and pharmacokinetics (PK). The trial included a screening phase, a treatment phase, and a post-treatment follow-up period. A long-term extension period is currently in place, allowing eligible patients to continue benefiting from the treatment.
About Erdafitinib
Erdafitinib is a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor approved for treating adults with unresectable or metastatic urothelial carcinoma with susceptible FGFR3 genetic alterations, particularly those who have previously received at least one line of PD-1 or PD-L1 inhibitor therapy. The drug is also under investigation in a Phase 1 study for patients with non-muscle invasive or muscle-invasive bladder cancer with selected FGFR alterations and in a Phase 3 study comparing it to intravesical chemotherapy in patients with intermediate-risk non-muscle invasive bladder cancer.
Regulatory Approvals and Future Development
In addition to the EC approval, erdafitinib received U.S. FDA approval in January 2024 for treating adults with locally advanced or metastatic urothelial carcinoma with FGFR3 genetic alterations whose disease has progressed following prior systemic therapy. Janssen Pharmaceutica NV, under an exclusive worldwide license and collaboration agreement with Astex Therapeutics Limited, is responsible for the development and commercialization of erdafitinib.
Understanding Urothelial Carcinoma and FGFR Testing
Urothelial carcinoma (UC), originating in the bladder's innermost lining, represents the majority of bladder cancers. Approximately 20% of patients with metastatic urothelial carcinoma exhibit FGFR genetic alterations, which are linked to increased tumor growth and survival. Testing for FGFR mutations and fusions can help identify patients eligible for FGFR-targeted therapies like erdafitinib. Early molecular and genomic testing, ideally conducted at the diagnosis of advanced bladder cancer, is recommended to facilitate timely treatment decisions and prevent delays in later therapy stages.
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