Erdafitinib
Indications
Erdafitinib is used for:
Urothelial Carcinoma
Adult Dose
Urothelial Carcinoma
Indicated for locally advanced or metastatic urothelial carcinoma that has fibroblast growth factor receptor-2 (FGFR2) or FGFR3 genetic alterations and progressed during or following at least 1 line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy
8 mg PO qDay initially; increase to 9 mg PO qDay based on serum phosphate (PO4) levels and tolerability at 14-21 days
Increase dose to 9 mg qDay if serum phosphate level <5.5 mg/dL and there are no ocular disorders or >Grade 2 adverse reactions
Continue until disease progression or unacceptable toxicity
Hepatic impairment
Mild (TB ?ULN and AST >ULN or TB >1 to 1.5x ULN and any AST): No clinically meaningful trends in the pharmacokinetics observed
Moderate or severe: Unknown
Child Dose
Renal Dose
Renal impairment
Mild or moderate (eGFR 30-89 mL/min/1.73 m²): No clinically meaningful trends in the pharmacokinetics observed
Severe or dialysis: Unknown
Administration
Contra Indications
Hypersensitivity
Precautions
Based on mechanism of action and animal studies, can cause fetal harm if administered to pregnant women
Ocular disorders
Can cause ocular disorders, including central serous retinopathy/retinal pigment epithelial detachment (CSR/RPED), resulting in visual-field defect
Perform monthly ophthalmological examinations during first 4 months of treatment and then every 3 months afterwards, and urgently at any time for visual symptoms
Dry eye symptoms are common; all patients should receive dry eye prophylaxis with ocular demulcents as needed
Hyperphosphatemia
Increases in serum phosphate levels are a pharmacodynamic effect as a consequence of FGFR inhibition
Median onset time for any grade event of hyperphosphatemia was 20 days
Monitor for hyperphosphatemia and follow dose modifications when required
Patients may require phosphate binders during treatment
Pregnancy-Lactation
Pregnancy
Based on the mechanism of action and findings in animal reproduction studies, can cause fetal harm when administered to pregnant women
Animal studies: Administration to pregnant rats during organogenesis caused malformations and embryofetal death at maternal exposures that were less than the human exposures at the maximum recommended human dose based on AUC
Pregnancy testing recommended for females of reproductive potential before initiating erdafitinib
Infertility: Based on findings in animal studies, may impair fertility in females of reproductive potential
Contraception
Females: Advise females of reproductive potential to use effective contraception during treatment and for 1 month after last dose
Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 1 month after last dose
Lactation
No data are available on presence in human milk, effects on breastfed children, or on milk production
Owing to potential serious adverse reactions in breastfed children, advise lactating women not to breastfeed during treatment and for 1 month following last dose
Interactions
CYP2C9 and CYP3A4 substrate; time-dependent CYP3A4 inhibitor and inducer; substrate and inhibitor of P-gp; OCT2 inhibitor
Strong CYP2C9 or CYP3A4 inhibitors
Coadministration increases erdafitinib plasma concentrations
If unable to avoid coadministration, consider lower erdafitinib dose
Strong CYP2C9 or CYP3A4 inducers
Coadministration may significantly decrease erdafitinib plasma concentrations and efficacy
Avoid coadministration
Moderate CYP2C9 or CYP3A4 inducers
Coadministration may significantly decrease erdafitinib plasma concentrations and efficacy
If moderate CYP2C9 or CYP3A4 inducer must be coadministered at start of treatment, administer 8-mg/day dose as recommended, with potential to increase to 9 mg/day based on serum phosphate levels on Days 14 to 21 and tolerability
If moderate CYP2C9 or CYP3A4 inducer must be coadministered after the initial dose increase period based on serum phosphate levels and tolerability, increase erdafitinib dose up to 9 mg
When a moderate inducer discontinued, continue erdafitinib at same dose, in absence of drug-related toxicity
Serum phosphate level-altering drugs
Coadministration with other serum phosphate level-altering agents may increase or decrease serum phosphate levels
Avoid coadministration before initial dose increase period (Days 14-21)
Adverse Effects
Side effects of Erdafitinib :
>10% (All Grades)
Phosphate increased (76%)
Stomatitis (56%)
Fatigue (54%)
Creatinine increased (52%)
Diarrhea (47%)
Dry mouth (45%)
ALT increased (41%)
Alkaline phosphatase increased (41%)
Onycholysis (41%)
Sodium decreased (40%)
Decreased appetite (38%)
Albumin decreased (37%)
Dysgeusia (37%)
Hemoglobin decreased (35%)
Dry skin (34%)
AST increased (30%)
Magnesium decreased (30%)
Constipation (28%)
Dry eye (28%)
Palmar-plantar erythrodysesthesia (26%)
Alopecia (26%)
Phosphate decreased (24%)
Abdominal pain (23%)
Calcium increased (22%)
Nausea (21%)
Musculoskeletal pain (20%)
Platelets decreased (19%)
Leukocytes decreased (17%)
Blurred vision (17%)
Paronychia (17%)
Urinary tract infection (17%)
Potassium increased (16%)
Weight decreased (16%)
Pyrexia (14%)
Vomiting (13%)
Nail discoloration (11%)
Conjunctivitis (11%)
Oropharyngeal pain (11%)
Hematuria (11%)
Arthralgia (11%)
>10% (Grades 3-4)
Sodium decreased (16%)
Mechanism of Action
Fibroblast growth factor receptor (FGFR) inhibitor; FGFRs are a family of receptor tyrosine kinases
In vitro, erdafitinib inhibits FGFR phosphorylation and signaling and decreases cell viability in cell lines expressing FGFR genetic alterations, including point mutations, amplifications, and fusions