Erdafitinib for the treatment of metastatic bladder cancer

ABSTRACT

Introduction: Since the approval of immune checkpoint inhibitors (ICIs), there has been continuing and significant progress in urothelial cancer (UC) treatment. However, only about one fifth of UC patients respond to ICI. Recently, erdafitinib was developed for treating locally advanced or metastatic UC (mUC) with FGFR3 or FGFR2 alterations, accounting for 15–20% of patients. Erdafitinib is the first targeted therapy ever approved for mUC.

Areas covered: This review summarizes the preclinical and clinical data on erdafitinib for UC. PubMed search and relevant articles presented at international conferences were used for the literature search.

Expert opinion: The FDA approval of erdafitinib provided a new treatment option for FGFR-altered UC progressing on platinum-based chemotherapy. It is not clear whether FGFR inhibitor is a preferred second-line treatment choice to ICI. Compared to ICI, erdafitinib has a better response rate in patients with visceral metastases. However, a shorter duration of response and toxicity profile of erdafitinib, particularly ocular toxicity, is an important consideration. Regular eye exams are recommended by the FDA. Tumor profiling during upfront therapy may help identify those who benefit at the time of progression. In summary, a high unmet need remains for new drugs in chemotherapy- and ICI-refractory UC.

KEYWORDS:

• Bladder cancer
• erdafitinib
• FGFR
• mutation
• FGFR3-TACC3 translocation
• urothelial carcinoma

Article Highlights

• Urothelial cancer is an aggressive cancer with poor prognosis, high mortality and low response rate to current standard treatment options.

• FGFR alterations are present in approximately 15–20% of advanced or mUC patients.

• Erdafitinib, a small-molecule tyrosine kinase inhibitor, was found to be a potent selective inhibitor of FGFR1–4.

• Erdafitinib was studied in preclinical and early phase clinical trials in patients with solid tumors, including locally advanced or metastatic urothelial cancer and was shown to have antitumor activity.

• In previously treated locally advanced or metastatic urothelial cancer patients with FGFR alterations, erdafitinib was demonstrated to have an objective response rate of 40% (37% partial response and 3% complete response).

• Response to erdafitinib was not shown to be affected by the presence of visceral metastasis.

• Among patients with FGFR mutations or fusions, a very low proportion had a response to previous immunotherapy.

• Caution is required with regards to adverse effects or erdafitinib, particularly with ocular toxicity.

Declaration of interest

J Bellmunt discloses being a Consultant and advisory board participant for Janssen, Bayer and Bioclin. Lecture fee from Janssen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.