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Erdafitinib for the treatment locally advanced or metastatic urothelial carcinoma in adult patients with susceptible FGFR3/FGFR2 genetic alterations and disease progression during or following at least one line of platinum-containing chemotherapy and within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

April 12, 2019, with PAP

On April 12, 2019, the Food and Drug Administration granted accelerated approval to erdafitinib (BALVERSA, Janssen Pharmaceutical Companies) for patients with locally advanced or metastatic urothelial carcinoma, with susceptible FGFR3 or FGFR2 genetic alterations, that has progressed during or following platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

Patients should be selected for therapy based on an FDA-approved companion diagnostic for erdafitinib. Today, the FDA also approved the therascreen® FGFR RGQ RT-PCR Kit, developed by QIAGEN, for use as a companion diagnostic for this therapeutic indication.

Erdafitinib approval was based on data from a cohort of 87 patients enrolled on Study BLC2001 (NCT02365597), a multicenter, open-label, single-arm trial. These patients had locally advanced or metastatic urothelial carcinoma that had progressed on or after at least one prior chemotherapy and had certain FGFR3 gene mutations or FGFR2 or FGFR3 gene fusions. Patients received erdafitinib at a starting dose of 8 mg once daily with a dose increase to 9 mg daily in those whose serum phosphate levels were below the target of 5.5 mg/dL, between days 14 and 17. The starting dose was increased to 9 mg daily in 41% of the patients. Erdafitinib was administered until disease progression or unacceptable toxicity.

The major efficacy outcome measure was objective response rate (ORR) as determined by blinded independent review committee according to RECIST 1.1. ORR was 32.2% (95% CI:22.4, 42.0), with complete responses in 2.3% and partial responses in 29.9%. Median response duration was 5.4 months (95% CI: 4.2, 6.9). Responders included patients who had previously not responded to anti PD-L1 or PD-1 treatment.

Erdafitinib can cause ocular disorders. Central serous retinopathy or retinal pigment epithelial detachment resulting in visual field defect was reported in 25% of patients. The most common adverse reactions reported in at least 40% of patients were increased serum phosphate, stomatitis, fatigue, increased serum creatinine, diarrhea, dry mouth, onycholysis, increased alanine aminotransferase, increased alkaline phosphatase, and decreased sodium.

The recommended initial dose of erdafitinib is 8 mg orally once daily (with or without food) with a dose increase to 9 mg daily if criteria are met (see above).

View full prescribing information for BALVERSA

This indication is approved under accelerated approval based on tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. FDA granted this application priority review and breakthrough therapy designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

Pharmacist’s Applications to Practice

Erdafitinib for the Treatment of Locally Advanced or Metastatic Urothelial Carcinoma in Adult Patients with Susceptible FGFR3/FGFR2 Genetic Alterations and Disease Progression During or Following at Least One Line of Platinum-Containing Chemotherapy and Within 12 Months of Neoadjuvant or Adjuvant Platinum-Containing Chemotherapy

Author: Kirollos S. Hanna, PharmD BCOP BCPS
Assistant Professor of Pharmacy, Mayo Clinic College of Medicine
Hematology/Oncology Clinical Pharmacist, University of Minnesota Medical Center
Minneapolis, MN

What is the potential role for erdafitinib in the treatment of urothelial carcinoma?

  • Erdafitinib, approved by the U.S. Food and Drug Administration in April 2019 (breakthrough designation was granted in March 2018), is the first fibrinoblast growth factor receptor (FGFR) kinase inhibitor approved as a second-line treatment option in patients with locally advanced or metastatic urothelial carcinoma (mUC) that expresses the genetic aberration. Currently, it is also the only oral treatment option for the treatment of urothelial carcinoma (UC).1
  • Systemic chemotherapy and immunotherapy with checkpoint inhibitors are options for treating locally advanced UC and mUC. Performance status (PS), renal function, comorbidities, and programmed death-ligand 1 (PD-L1) expression are determinants for the selection of appropriate frontline treatments. Patients able to tolerate platinum-based chemotherapy should receive this option in the frontline setting because of improved response and survival rates compared to patients who receive checkpoint inhibitors and exhibit low PD-L1 expression. Pembrolizumab and atezolizumab are first-line therapies for cisplatin-ineligible patients with PD-L1 expression in tumors. PD-L1 expression is defined as a combined positive score of 10 or higher for pembrolizumab and PD-L1 stained tumor-infiltrating immune cells covering 5% or more of the tumor area for atezolizumab; either agent may be used for patients deemed ineligible for any platinum-containing therapy regardless of PD-L1 expression. Following disease progression on frontline therapy, second-line treatment options are influenced by prior therapy, PS, and immunogenicity.2,3
  • FGFRs are widely distributed transmembrane tyrosine kinase receptors, and receptor aberrations are common in a wide variety of cancers, with the majority being gene amplifications or activating mutations. They are involved in development, differentiation, cell survival, migration, angiogenesis, and carcinogenesis.4 In humans, four FGFRs (FGFR1–4) share structural homology with vascular endothelial growth factor receptors, platelet-derived growth factor receptors, and other tyrosine kinase receptors. FGFRs signal through several intracellular pathways, including the Ras/Raf/MEK and the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)–Akt pathway. Overall, FGFR alterations occur in 10%–20% of mUC cases and are enriched in immunologically “cold” luminal 1 subtype UC.5,6
  • The efficacy and safety of erdafitinib in UC was established from the BLC2001 trial, a multicenter open-label single-arm study.1
    • Population: 87 patients with locally advanced UC or mUC with an FGFR gene mutation or fusion following at least one prior therapy
      • Median age: 67 years; 79% male; 74% Caucasian
      • Ninety-two percent of patients exhibited a PS of 1 or higher, and 66% of patients had visceral metastases.
      • Ninety-seven percent of patients had received previous platinum-based therapy with either cisplatin or carboplatin.
        • Prior cisplatin-based regimen only: 56%
        • Prior carboplatin-based regimen only: 29%
        • Both cisplatin- and carboplatin-based regimens: 10%
      • Three percent of patients had disease progression following prior platinum-containing neoadjuvant or adjuvant therapy only.
      • Twenty-four percent of patients had been treated with prior anti-PD-L1/PD-1 therapy.
    • Intervention: starting dose for erdafitinib of 8 mg once daily, with a dose increase to 9 mg daily in those whose serum phosphate levels were below the target of 5.5 mg/dL between days 14 and 17. The dose was increased for 41% of patients.
    • Efficacy outcomes
      • Overall response rate (ORR) in entire population: 32.2%
        • ORR FGFR3 point mutation: 40.6%
        • ORR FGFR fusion: 11.1%
        • ORR FGFR2 fusion: 0%
      • Median duration of response: 5.4 months
    • Safety outcome (over 20%; any grade): phosphate increased (76%), stomatitis (56%), fatigue (54%), creatinine increased (52%), diarrhea (47%), dry mouth (45%), onycholysis (41%), alanine aminotransferase increased (41%), alkaline phosphatase increased (41%), sodium decreased (40%), decreased appetite (38%), albumin decreased (37%), dysgeusia (37%), hemoglobin decreased (35%), dry skin (34%), aspartate aminotransferase increased (30%), magnesium decreased (30%), dry eye (28%), constipation (28%), alopecia (26%), palmar-plantar erythrodysesthesia syndrome (26%), phosphate decreased (24%), abdominal pain (23%), calcium increased (22%), nausea (21%), and musculoskeletal pain (20%).
  • A phase 3 trial (NCT03390504) is comparing erdafitinib versus standard of care, consisting of chemotherapy (docetaxel or vinflunine) or pembrolizumab, in participants with advanced UC and selected FGFR aberrations whose disease has progressed on or after one prior line of systemic therapy.7 The primary endpoint of the study is overall survival (OS), with a planned completion date of November 2020.
  • The NCCN guidelines recommend erdafitinib as an alternative preferred treatment option (Category-2A recommendation) in the second-line setting for locally advanced UC or mUC in patients with select FGFR genetic aberrations.3

What role can the pharmacist play in the management of patients on erdafitinib?

  • The recommended initial dose of erdafitinib is 8 mg orally once daily taken with or without food. Between days 14 and 21 of cycle 1, the dose should be increased to 9 mg once daily as long as serum phosphate levels remain below 5.5 mg/dL. Phosphate levels should be monitored monthly.1
  • Dose reduction schedule: From 9 mg: 8 mg, 6 mg, 5 mg, 4 mg, discontinue (each increment is 1 level).
  • No dosage adjustments are provided in the manufacturer’s labeling for baseline hepatic or renal impairment; impairment does not alter erdafitinib pharmacokinetics; therefore, dosage adjustment is not likely necessary. Erdafitinib pharmacokinetics have not been studied in severe renal impairment or in moderate-to-severe hepatic impairment.
  • If serum phosphate level is greater than 7.0 mg/dL, an oral phosphate binder may be used until the level is less than 5.5 mg/dL. Daily intake of phosphate should be restricted to 600–800 mg per day.
  • Additionally, dose adjustments may be required for hyperphosphatemia:
    • 5.6–6.9 mg/dL (1.8–2.3 mmol/L): Continue therapy with erdafitinib.
    • 7.0–9.0 mg/dL (2.3–2.9 mmol/L): Interrupt erdafitinib therapy. Assess weekly and resume normal dose when serum phosphate level reaches 5.5 mg/dL or baseline; may dose-reduce by one level if phosphate level is abnormal for more than 1 week.
    • Above 9.0 mg/dL (above 2.9 mmol/L): Interrupt erdafitinib therapy. Assess weekly and resume at one dose level lower when serum phosphate level is less than 5.5 mg/dL or baseline.
    • Above 10.0 mg/dL (above 3.2 mmol/L) or when significant impairment in renal function or Grade 3 hypercalcemia occurs: Interrupt erdafitinib therapy. Assess weekly and resume at two dose levels lower when serum phosphate level is less than 5.5 mg/dL or baseline.
  • Erdafitinib is metabolized via CYP2C9 and CYP3A4. If strong inhibitors cannot be avoided, monitor for increased toxicities. Avoid concomitant use of the drug with strong inducers and increase the dose up to 9 mg if it is used with moderate inducers.
  • If a dose of erdafitinib is missed, it may be taken as soon as possible on the same day and the normal schedule resumed the following day.
  • Ocular dryness occurs in approximately one third of patients. All patients should receive dry-eye prophylaxis with ocular demulcents as needed.
    • Patients should be advised to undergo monthly ophthalmological exams for the first four cycles and every 3 months afterward.
    • Any ocular symptoms should be addressed urgently.
    • Serous retinopathy or retinal pigment epithelial detachment may require dose interruption, dose reduction, and/or discontinuation of therapy.

Clinical Pearls

  • Erdafitinib is available in 3-mg, 4-mg, and 5-mg tablets and is supplied in these ways:1
    • 3 mg: bottle and dose pack of 56 and 84 tablets
    • 4 mg: bottle of 56 and 84 tablets, starter pack of 14 tablets, dose pack of 28 and 56 tablets
    • 5 mg: bottle and dose pack of 28 tablets.
  • Erdafitinib should be stored at room temperature and handled as hazardous.
  • A gap exists in optimal treatment selection for second-line mUC following disease progression on platinum-based chemotherapy. Pembrolizumab is the only Category-1 recommendation based on findings from the Keynote 045 trial demonstrating OS benefit over chemotherapy regardless of PD-L1 expression. Erdafitinib is a category-2A recommendation in patients with the FGFR aberrations and is the only oral treatment option. These patients are technically eligible for pembrolizumab, so findings from the ongoing phase 3 trial (NCT03390504) comparing erdafitinib with standard of care, consisting of chemotherapy or pembrolizumab, will help close this practice gap.3,7,8
  • Copay assistance for erdafitinib is available through the Janssen Prescription Assistance Program.9


  1. Balversa (erdafitinib) [prescribing information]. Horsham, PA: Janssen Products; April 2019. Available at
  2. Suzman DL, Agrawal S, Ning YM, et al. FDA approval summary: atezolizumab or pembrolizumab for the treatment of patients with advanced urothelial carcinoma ineligible for cisplatin-containing chemotherapy. Oncologist. 2019;24(4):563-569.
  3. National Comprehensive Cancer Network. Bladder Cancer (Version 3.2019). Available at Accessed April 29, 2018.
  4. Katoh M, Nakagama H. FGF receptors: cancer biology and therapeutics. Med Res Rev. 2014;34:280-300.
  5. Gust KM, McConkey DJ, Awrey S, et al. Fibroblast growth factor receptor 3 is a rational therapeutic target in bladder cancer. Mol Cancer Ther. 2013;12:1245-1254.
  6. Siefker-Radtke AO, Necchi A, Park SH, et al. First results from the primary analysis population of the phase 2 study of erdafitinib (ERDA; JNJ-42756493) in patients (pts) with metastatic or unresectable urothelial carcinoma (mUC) and FGFR alterations (FGFRalt). J Clin Oncol. 2018;36(suppl 15):4503. Available at
  7. U.S. National Library of Medicine. 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 April 29, 2019.
  8. Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med. 2017;376(11):1015-1026.
  9. Janssen Prescription Assistance Program. Available at Accessed April 29, 2019.