Overview of the clinical use of erdafitinib as a treatment option for the metastatic urothelial carcinoma: where do we stand

ABSTRACT

Introduction

Erdafitinib is the first orally administered pan-fibroblast growth factor receptor (FGFR) kinase inhibitor approved by the Food and Drug Administration (FDA).

Areas covered

Specifically binding to FGFR family (FGFR-1 to FGFR-4), erdafitinib leads to reduced cell signaling and cellular apoptosis. Coupled with the ability to bind to vascular endothelial growth factor 2 (VEGFR-2), KIT, Fms-related tyrosine kinase 4 (FLT4), platelet-derived growth factor receptor α and β (PDGFR-α and PDGFR-β), RET and colony-stimulating factor 1 receptor (CSF-1 R), erdafitinib has further reported antitumor features causing cell killing.

Expert opinion

In this review, we provide a comprehensive overview of erdafitinib chemical structure, pharmacologic properties, and current knowledge of clinical efficacy in the treatment of locally advanced or metastatic urothelial carcinoma. This treatment, recently approved in the U.S., is available for adult patients harboring FGFR2/FGFR3 genetic alterations who progressed within 12 months of an adjuvant or neoadjuvant chemotherapy regimen including platinum or progressed during or after prior a chemotherapy regimen including platinum.

KEYWORDS:

• Urothelial carcinoma
• solid tumors
• genitourinary cancer therapy
• erdafitinib
• toxicity
• pan-FGFR inhibitors
• bladder cancer therapy
• FGFR mutations

Article highlights

• Urothelial cancer is an aggressive malignancy with significant mortality, unsatisfactory response rate to current baseline therapies, and grave prognosis.

• Up to 20% of mUC patients are diagnosed with FGFR genomic alterations.

• Erdafitinib is a novel tyrosine kinase inhibitor with confirmed potent selective inhibition of FGFR1-4 and antitumor activity against locally advanced or metastatic urothelial cancer.

• Erdafitinib has shown an objective response rate of 40% among previously treated urothelial cancer patients (locally advanced or metastatic stage) with FGFR susceptibility.

• Ocular toxicity is the most dangerous adverse event correlated with the administration of erdafitinib.

• Several FGFR inhibitors are being investigated in separate ongoing trials – alone or in combination with other agents.

Declaration of interest

Authors have no 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 including employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer has disclosed being on the advisory board of Pfizer, BMS, Genentech, EMD Serono, Novartis, Merck, Sanofi, Seattle, Genetics/Astellas, AstraZeneca, Exelixis, Janssen, Amgen, Eisai, and Bicycle Therapeutics. They have also disclosed receiving speaking fees for Physicians Education Resource (PER), Onclive, Research to Practice, and Clinical Care Options. They have also received research support from Boehringer-Ingelheim, Bayer, Pfizer, Merck, Sanofi, and AstraZeneca. They have also disclosed being a member of the steering committee of trials for BMS, Bavarian Nordic, Seattle Genetics, QED, AstraZeneca and Debiopharm. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper did not receive any funding.