Erdafitinib (Balversa) is a fibroblast growth factor receptor kinase inhibitor that is indicated for the treatment of patients with locally advanced or metastatic urothelial cancer with susceptibility to FGFR gene mutations.

Erdafitinib Uses:

• Urothelial carcinoma, locally advanced or metastatic:

  • For advanced or metastatic urothelial carcinoma in adults in whom:
    • Susceptibility to FGFR3 or FGFR2 genetic alterations present and
    • The disease spread despite receiving platinum-based therapy including use within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy

Erdafitinib (Balversa) Dose in Adults

Note: phosphate restriction to 600 to 800 mg/day, repeat levels 2-3 weeks after treatment initiation.

Erdafitinib (Balversa) Dose in the treatment of locally advanced or metastatic urothelial carcinoma (with susceptible FGFR genetic alteration):

• Oral: Initial: 8 mg once daily repeat serum phosphate after 2,3 weeks is <5.5 mg/dL (and no ocular disorders or ≥ grade 2 toxicity), increase dose to 9 mg once daily according to tolerance.
• Continue until disease progression or until unacceptable toxic adverse effects develop.

• Missed or vomited doses:

  • If a dose is missed can be taken again as soon as remembered. Dose need not be replaced if vomiting occurs.

Use in Children:

Not indicated.

Erdafitinib (Balversa) Pregnancy Category: X

• Fetal harm can be caused by erdafitinib. It is important to rule out pregnancy before you start treatment. 
• Therapy should be completed within one month of completion. Male patients and their female partners must avoid pregnancy.

Use of Erdafitinib while breastfeeding

• Breastfeeding is not recommended for infants during treatment or up to one month after last erdafitinib dosage.

Erdafitinib (Balversa) Dose in Kidney Disease:

• eGFR 30 to 89 mL/minute/1.73 m²:

  • No dose adjustment needed.

• eGFR <30 mL/minute/1.73 m²:

  • No dose adjustment needed.

• ESRD requiring dialysis:

  • No dose adjustment needed.

Erdafitinib (Balversa) Dose in Liver disease:

• Mild impairment (total bilirubin ≤ ULN and AST > ULN or total bilirubin >1 to 1.5 times ULN and any AST): 
  • No dose adjustment needed.
• Moderate or severe impairment: 
  • No dose adjustment recommended.

Common Side Effects of Erdafitinib (Balversa):

• Central Nervous System:

  • Fatigue

• Dermatologic:

  • Onycholysis
  • Xeroderma
  • Alopecia
  • Palmar-Plantar Erythrodysesthesia
  • Paronychia
  • Nail Discoloration

• Endocrine & Metabolic:

  • Hyperphosphatemia
  • Decreased Serum Sodium
  • Decreased Serum Albumin
  • Decreased Serum Magnesium
  • Decreased Serum Phosphate
  • Increased Serum Calcium
  • Increased Serum Potassium
  • Weight Loss

• Gastrointestinal:

  • Stomatitis
  • Diarrhea
  • Xerostomia
  • Decreased Appetite
  • Dysgeusia
  • Constipation
  • Abdominal Pain
  • Nausea
  • Vomiting

• Genitourinary:

  • Urinary Tract Infection
  • Hematuria

• Hematologic & Oncologic:

  • Decreased Hemoglobin
  • Decreased Platelet Count
  • Decreased White Blood Cell Count

• Hepatic:

  • Increased Serum Alanine Aminotransferase
  • Increased Serum Alkaline Phosphatase
  • Increased Serum Aspartate Aminotransferase

• Neuromuscular & Skeletal:

  • Musculoskeletal Pain
  • Arthralgia

• Ophthalmic:

  • Dry Eye Syndrome
  • Retinal Pigment Epithelium Detachment
  • Retinopathy
  • Blurred Vision
  • Conjunctivitis

• Renal:

  • Increased Serum Creatinine

• Respiratory:

  • Oropharyngeal Pain

• Miscellaneous:

  • Fever

Less Common Side Effects of Erdafitinib (Balversa):

• Hematologic & oncologic:

  • Increase in fasting plasma glucose
  • Decreased neutrophils

• Ophthalmic:

  • Increased lacrimation

• Respiratory:

  • Dyspnea

• Neuromuscular & skeletal:

  • Asthenia

Contraindication to Erdafitinib (Balversa):

• The manufacturer's labeling does not list any contraindications.

Warnings and precautions

• Hyperphosphatemia

  • Therapy may cause hyperphosphatemia. Monitor your levels during treatment. You may need to adjust the dose or withhold treatment if you use phosphate binders.
  • Limit your dietary intake. Limit your intake of agents that can increase serum phosphate (eg, potassium-phosphate or Vitamin D supplements, antiacids, laxatives or phosphate-containing medications, etc.)

• Ocular toxicities:

  • One-fourth of patients with central serous retinopathy/retinal color epithelial detached (CSR/RPED), were reported to have it in a clinical study, which included grade 3 events. Average onset at 50 days, transient in 13%, and permanent in 1%
  • CSR/RPED can cause visual field defects including central field defects.
  • If symptoms don't improve within a month, you can continue therapy.
  • Dry eye symptoms were reported in more than one quarter of patients, with grade 3 events included. If necessary, administer dry eye prophylaxis (with or without ocular demulcents).
  • Complete eye exams at baseline, monthly for the first four months, then every three months and as often as clinically necessary.
  • Ocular toxicities can be treated with a dose adjustment, withholding, or even stopping.

Erdafitinib: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• susceptibility to FGFR genetic alteration
• serum phosphate level at baseline, initially after 2 to 3 weeks, then monthly then as needed
• Rule out pregnancy before starting treatment
• an eye examination at baseline, once monthly for the first 4 months, then every 3 months or as needed
• Close observation in patients with known or suspected CYP2C9*3/*3 genotype
• Monitor compliance.

How to administer Erdafitinib (Balversa)?

Oral: Administer with or without food; swallow whole, do not break or chew.

Mechanism of action of Erdafitinib (Balversa):

• Erdafitinib inhibits fibroblast growth factor receptor (FGFR), FGFR2, FGFR3, FGFR4 enzyme activities and is a fibroblast-growth factor receptor (FGFR). 
• Erdafitinib binds also to RET, CSF1R and PDGFRA.This results in decreased FGFR-related signals and decreased cell viability for cell lines expressing FGFR genetic alterations.

Protein binding:

• 99.8%, primarily to alpha-1-acid glycoprotein

Metabolism:

• Primarily hepatic by CYP2C9 and CYP3A4

Half-life elimination:

• 59 hours

Time to peak:

• 2.5 hours (range: 2 to 6 hours)

Excretion:

• Feces: ~69% (19% as unchanged drug);
• urine: 19% (13% as unchanged drug).

International Brand Names of Erdafitinib:

• Balversa

Erdafitinib Brand Names in Pakistan:

No Brands Available in Pakistan.