The current standard of care for the majority of patients with advanced urothelial carcinoma includes cisplatin-based chemotherapy followed by immunotherapy with a PD-1 or PD-L1 inhibitor. While this treatment approach is highly effective in some patients, the majority of patients do not respond to immunotherapy and treatment options for these patients are extremely limited. As many as 20% of patients with advanced urothelial cancer carry alterations in the gene for fibroblast growth factor receptor (FGFR), which is associated with lower sensitivity to immunotherapy. Erdafitinib is a pan-FGFR inhibitor that has demonstrated activity in patients with FGFR alterations in a phase I trial. This agent recently became the first targeted therapy approved by the FDA for the treatment of advanced urothelial cancer on the strength of preliminary results from the phase II BLC2001 trial. Full results for this study have now been published in The New England Journal of Medicine.
The trial evaluated the safety and efficacy of erdafitinib in 99 patients with urothelial cancer who carried alterations in FGFR and had progressed on at least one course of chemotherapy. Prior treatment with immunotherapy was allowed. At a median follow-up of 11.2 months, the confirmed objective response rate to erdafitinib was 40%, including complete response (CR) in 3% of patients. In patients who had received prior treatment with immunotherapy, the ORR was 59%. The historical standard ORR with taxane chemotherapy in this population is approximately 10%. The median duration of response was 5.6 months, with approximately 30% of responders remaining in response for more than 12 months. The median progression-free survival (PFS) was 5.5 months, and median overall survival (OS) was 13.8 months.
A total of 46% of patients experienced grade 3 or higher treatment-related adverse events (AEs), the majority of which were easily managed with dose reductions. Only 13% of patients discontinued treatment due to AEs. The most common grade 3 or higher AEs included hyponatremia (11%), stomatitis (10%), and asthenia (7%).
The investigators concluded that erdafitinib is associated with measurable clinical benefit in patients with advanced urothelial carcinoma with FGFR alterations and should be considered a new treatment option for appropriate patients following progression on chemotherapy and/or immunotherapy. While the FDA granted accelerated approval for erdafitinib in patients with FGFR alterations on the strength of these data, full approval will be contingent upon a confirmatory phase III trial.
Read more about this study on Medscape Oncology.