Research in context
Evidence before this study
We searched PubMed for clinical trials of fibroblast growth factor receptor (FGFR) inhibitors used to treat patients with urothelial cancer or bladder cancer, using the terms “bladder cancer” OR “urothelial cancer” AND “fibroblast growth factor receptor,” published from Jan 1, 2010, to Jan 1, 2021, with limits for clinical trials and no language restrictions. At the time of the initial protocol approval for the phase 2 BLC2001 study of erdafitinib (Jan 19, 2015), our searches identified one published report of a clinical trial of an FGFR inhibitor (dovitinib in combination with gemcitabine plus cisplatin or carboplatin) in patients with advanced solid tumours, in which the combination was poorly tolerated. At that time, systemic treatment for metastatic urothelial carcinoma was generally unsatisfactory and had remained unchanged for several decades. More recently, approved anti-PD-(L)1 agents provided a small improvement in response rates over traditional chemotherapy and were accompanied by immune-related adverse events that were potentially serious and sometimes fatal. Differential responses to anti-PD-(L)1 agents have been observed in different bladder cancer subtypes based on gene expression and histopathology and their underlying immune microenvironment. The primary analysis of BLC2001 was published in 2019 and, on the basis of these data, erdafitinib was the first targeted therapy approved by the US Food and Drug Administration for treatment of patients with locally advanced or metastatic urothelial carcinoma and prespecified FGFR alterations. Erdafitinib is now included in the National Comprehensive Cancer Network and European Society for Medical Oncology guidelines as an option for second-line treatment of patients with locally advanced or metastatic urothelial cancer.
Added value of this study
Our findings show that, with longer follow-up, erdafitinib treatment continues to show consistent clinical benefits for patients with locally advanced or metastatic urothelial cancer who have tumours with specific FGFR alterations, and that erdafitinib has a manageable safety profile.
Implications of all the available evidence
The long-term follow-up of this study confirms the benefit of erdafitinib, an FGFR inhibitor, for the treatment of patients with locally advanced or metastatic urothelial cancer and specific FGFR alterations. Further research, in a randomised, controlled, phase 3 study in patients with advanced urothelial cancer, is ongoing to evaluate erdafitinib as second-line monotherapy compared with a PD-1 inhibitor or chemotherapy. Another study is ongoing to evaluate erdafitinib in combination with a PD-1 inhibitor (cetrelimab) in first-line treatment of patients with metastatic urothelial carcinoma who are ineligible for cisplatin.