By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

Drs. Elliott and Chan report no financial relationships relevant to this field of study.

The FDA has approved the first targeted therapy for metastatic bladder cancer. Erdafitinib is a kinase inhibitor that targets genetic alterations of certain fibroblast growth factor receptors (FGFRs). These regulate biological processes, including cell growth and division.1 Erdafitinib received breakthrough therapy status and accelerated approval based on tumor response rate. Further clinical trial data are required to confirm the clinical benefit of erdafitinib. It is marketed as Balversa.


Erdafitinib should be used to treat locally advanced or metastatic urothelial (transitional cell) carcinoma with susceptible FGFR3 or FGFR2 genetic alterations in patients who progressed during or following at least one course of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.1 Patient selection should be based on an FDA-approved companion diagnostic device (therascreen FGFR RGQ RT-PCR Kit).


The recommended initial dose is 8 mg (2 × 4 mg) orally once daily with a dose increase to 9 mg (3 × 3 mg) once daily based on serum phosphate levels and tolerability at 14 to 21 days.2 Treatment should be continued until disease progression or unacceptable toxicity. Dose modification/reduction is recommended because of adverse reactions (e.g., hyperphosphatemia, ocular disorders).2 Erdafitinib is available as 3 mg, 4 mg, and 5 mg tablets.


Erdafitinib offers the first targeted therapy for bladder cancer patients with susceptible FGFR mutations.


Erdafitinib can cause central serous retinopathy/retinal pigment epithelial detachment, resulting in visual field defect.2 This was reported in 25% of treated patients. Regular ophthalmological examination is recommended. Hyperphosphatemia was reported in 76% of patients.2 Thirty-two percent of patients received phosphate binders during treatment. Erdafitinib may cause embryo-fetal toxicity. Erdafitinib causes a wide variety of adverse events involving numerous organ systems and laboratory abnormalities.2 Grade 3 or higher adverse events include stomatitis (9%), hand-foot syndrome (6%), hyponatremia (16%), and onycholysis (10%). Erdafitinib can produce significant drug-drug interactions with strong/moderate CYP2C9 and CYP3A4 inhibitors and inducers as well as drugs that are substrates for these isoenzymes and transporters such as organic anion transporter 2 and P-glycoprotein.


The efficacy and safety of erdafitinib were evaluated in an open-label, single-arm study that included 87 subjects with locally advanced or metastatic urothelial carcinoma.2 Subjects were screened for FGFR3 gene mutations or FGFR gene fusions. Dosing started at 8 mg daily and increased to 9 mg once daily in subjects with serum phosphate levels below the target of 6.5 mg/dL between days 14 and 17. Erdafitinib was continued until disease progression or unacceptable toxicity. The primary efficacy endpoint was objective response rate (ORR) and duration of response (DoR) based on the RECIST v1.1 criteria determined by a blinded independent review committee. RECIST is a standardized measurement of solid tumor burden assessed primarily by imaging (e.g., MRI, CT).3 Ninety-seven percent of subjects received at least one course of cisplatin or carboplatin previously. Twenty-four percent had been treated with an anti-PDL1/PD-1 agent (i.e., checkpoint inhibitors). The ORR rate was 32.2%, with 29.9% as partial response. Results were better with FGFR3 mutations (40.6% vs. 11.1% for FGFR3 fusion).


Bladder cancer is the sixth most common cancer in the United States.1 Up to 21% of locally advanced or metastatic urothelial carcinomas have FGFR alterations, which is considered the third highest mutated cancer.1,4 Platinum-based chemotherapy has been the standard of care for advanced or metastatic bladder cancer. Checkpoint inhibitors (e.g., atezolizumab, pembrolizumab), which act by “releasing the brakes” on the immune system, have been approved for patients who have progressed during or after platinum-based chemotherapy, who are not eligible for cisplatin-containing chemotherapy, and whose tumors expressed PD-L1 or are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. Erdafitinib offers a potential option for those with susceptible mutations who have progressed on platinum therapy or on a checkpoint inhibitor or when the latter is not an option. A clinical trial is currently in progress that compares erdafitinib with docetaxel or vinflunine (not available in the United States) or pembrolizumab in participants with advanced urothelial cancer and selected FGFR mutatons.5 The estimated completion date is November 2020. The cost of therapy is $20,160 for a 28-day supply of 8 mg, $22,680 for a 28-day supply of 9 mg.


  1. U.S. Food & Drug Administration. FDA approves first targeted therapy for metastatic bladder cancer. April 12, 2019. Available at: Accessed May 28, 2019.
  2. Janssen Products, LP. Balversa Prescribing Information, April 2019. Available at: Accessed May 28, 2019.
  3. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-247.
  4. Nadal R, Bellmunt J. Management of metastatic bladder cancer. Cancer Treat Rev 2019;76:10-21.
  5. A Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Participants With Advanced Urothelial Cancer and Selected Fibroblast Growth Factor Receptor (FGFR) Gene Aberrations. Available at: Accessed May 28, 2019.