Erdafitinib, a potent inhibitor of fibroblast growth factor receptors (FGFR)-1, FGFR-2, FGFR-3, and FGFR-4, is an antineoplastic agent.1, 2, 5, 8
Erdafitinib is used for the treatment of adults with locally advanced or metastatic urothelial carcinoma with susceptible fibroblast growth factor receptor ( FGFR-3 ) genetic alterations that has progressed during or following at least one prior systemic therapy.1 An FDA-approved companion diagnostic test (e.g., Qiagen therascreen ® FGFR RGQ RT-PCR Kit) is required to confirm the presence of susceptible FGFR-3 genetic alterations in tumor specimens prior to initiation of therapy.1 Erdafitinib is not recommended for the treatment of patients who are eligible for and have not received prior programmed cell death (PD)-1 or programmed death-ligand 1 (PD-L1) inhibitor therapy.1
The current indication for erdafitinib was initially based principally on the results of an open-label, multicenter, noncomparative, phase 2 study (BLC2001) in patients with relapsed or refractory locally advanced or metastatic urothelial carcinoma.1, 2, 3, 9 In the BLC2001 study, the cohort of patients with relapsed or refractory advanced urothelial carcinoma included 87 adults with locally advanced or metastatic urothelial carcinoma that had progressed during or following at least one prior chemotherapy regimen.1, 2, 3 Patients enrolled in this cohort also had disease harboring at least one of the following FGFR genomic aberrations (as detected by a Clinical Trial Assay [CTA]): FGFR3 gene mutation (mutations at codon R248C, S249C, G370C, and/or Y373C) and/or gene fusion ( FGFR3-TACC3 , FGFR3-BAIAP2L1 , FGFR2-BICC1 , and/or FGFR2-CASP7 ).1 Erdafitinib was administered at an initial dosage of 8 mg orally once daily followed by an increase to 9 mg once daily if serum phosphate concentrations remained below 5.5 mg/dL on days 14-17 during cycle 1; an increase in dosage to 9 mg once daily was achieved in 41% of patients.1 Erdafitinib therapy was continued until disease progression or unacceptable toxicity occurred.1 The median age of patients enrolled in the relapsed or refractory cohort of this study was 67 years (range: 36-87 years); 79% were male, 74% were white, 92% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and 66% had visceral metastases.1 Most (97%) patients enrolled in the cohort had previously received at least one carboplatin- or cisplatin-containing therapy, 10% had received both carboplatin- and cisplatin-containing therapy, and 24% had previously received an anti-PD-1 or anti-PD-L1 monoclonal antibody.1
At the time of analysis, the objective response rate for patients in the relapsed or refractory disease cohort of this study was 32.2% with a median duration of response of 5.4 months; complete response was achieved in 2.3% of patients.1 In an exploratory subgroup analysis, the objective response rate in patients with FGFR-3 point mutation, FGFR-3 gene fusion, or FGFR-2 gene fusion was 40.6, 11.1, or 0%, respectively.1, 3 These response rates appeared to represent measurable benefits with erdafitinib treatment based on historical objective responses of approximately 10-20% with second-line, single-agent chemotherapy (e.g., taxanes, immune checkpoint inhibitors [e.g., pembrolizumab]) in patients with locally advanced and unresectable or metastatic urothelial carcinoma with FGFR aberrations.2, 3
In a confirmatory, phase 3, randomized, open-label, multicenter, 2-cohort trial (THOR), the efficacy of erdafitinib was evaluated in patients with previously treated metastatic urothelial carcinoma.1, 15 In Cohort 1, 266 adult patients with advanced urothelial cancer harboring selected FGFR-3 alterations were randomly assigned to erdafitinib 8 mg, with titration up to 9 mg, or chemotherapy (docetaxel 75 mg/m2 once every 3 weeks or vinflunine [not available in the United States] 320 mg/m2 once every 3 weeks) until unacceptable toxicity or progression.1, 15 All patients had disease progression after 1 or 2 prior treatments, at least 1 of which included a PD-1 or PD-L1 inhibitor.1, 15 The primary endpoint was overall survival, defined as the time from randomization to death from any cause.15 Key secondary efficacy outcome measures included progression-free survival and objective response rate assessed by the investigator using RECIST (Response Evaluation Criteria in Solid Tumors) Version 1.1.1, 15
The median age of enrolled patients was 67 years (range, 32-86 years); 71% were male; 54% were white, 29% Asian, and 0.4% Black.1, 15 Most patients had a baseline ECOG performance status of 0 (43%) or 1 (48%).1, 15 Eighty-one percent of patients had FGFR-3 mutations, 17% had fusions, and 2% had both mutations and fusions.1, 15 The majority (88%) of patients received platinum-containing chemotherapy previously.1 Results revealed that median overall survival was significantly improved with erdafitinib as compared to chemotherapy (12.1 versus 7.8 months), at a median follow-up of 15.9 months.1, 15 Median progression-free survival was also significantly longer with erdafitinib (5.6 versus 2.7 months), and investigator-assessed objective response rate was significantly higher with erdafitinib therapy (45.6% vs. 11.5%).1, 15
Cohort 2 of the THOR trial involved 351 adults with locally advanced or metastatic urothelial carcinoma with selected FGFR-3 alterations who received a single prior line of systemic therapy and were PD-1/PDL1 inhibitor naïve.1, 16 Patients were randomly assigned to erdafitinib 8 mg once daily, with titration up to 9 mg, or pembrolizumab 200 mg every 3 weeks.1, 16 The primary endpoint was overall survival; however, the study did not meet its major efficacy outcome measure for superiority of overall survival at the pre-specified final analysis.1, 16 Median overall survival was 10.9 months for erdafitinib as compared to 11.1 months for pembrolizumab.1, 16
The European Society of Medical Oncology (ESMO) released updated guidelines on the treatment of advanced urothelial carcinoma in 2024.17 ESMO recommends administration of enfortumab vedotin in combination with pembrolizumab as first-line therapy for treatment-naïve advanced or metastatic urothelial carcinoma, irrespective of platinum eligibility.17 If progression occurs on enfortumab vedotin in combination with pembrolizumab, standard platinum-based chemotherapy without maintenance avelumab in unselected patients or erdafitinib in selected FGFR -altered tumors can be recommended.17
If administration of enfortumab vedotin plus pembrolizumab is not possible, ESMO recommends nivolumab + cisplatin + gemcitabine or platinum-based chemotherapy + maintenance avelumab as alternative regimens.17 Erdafitinib is also recommended in patients with selected FGFR DNA fusions and mutations who have previously been treated with chemotherapy and an immune checkpoint inhibitor.17
Erdafitinib is administered orally once daily without regard to meals.1 The tablets should be swallowed whole.1
If a dose of erdafitinib is missed, take the dose as soon as possible on the same day and resume the regular dosing schedule the next day.1 If vomiting occurs at any time following administration of erdafitinib, a replacement dose should not be administered; take the next dose at the regularly scheduled time.1
Store between 20-25°C (excursions permitted between 15-30°C).1
For the treatment of locally advanced or metastatic urothelial carcinoma with susceptible FGFR-3 genetic alterations that has progressed during or following at least one prior systemic therapy in adults, the recommended initial dosage of erdafitinib is 8 mg orally once daily; if this initial dosage is tolerated (i.e., serum phosphate concentrations less than 9 mg/dL, absence of ocular disorders or grade 2 or greater adverse effects) for 14-21 days, the dosage of erdafitinib should be increased to a maximum dosage of 9 mg once daily.1 If phosphate level ≥9 mg/dL, follow the relevant dose modifications in Table 2.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1
Dosage Modification for Toxicity
If adverse reactions occur during erdafitinib therapy, temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of the drug may be necessary.1 If dosage modification is required, the dosage of erdafitinib should be reduced as described in Table 1.1
Dose Reduction Level | Current Dosage of 8 mg Daily | Current Dosage of 9 mg Daily |
|---|---|---|
First | Restart at 6 mg daily | Restart at 8 mg daily |
Second | Restart at 5 mg daily | Restart at 6 mg daily |
Third | Restart at 4 mg daily | Restart at 5 mg daily |
Fourth | Discontinue erdafitinib | Restart at 4 mg daily |
Fifth | Discontinue erdafitinib |
If hyperphosphatemia (≥7 mg/dL) occurs during erdafitinib therapy, temporary interruption, dosage reduction, and/or permanent discontinuance of the drug may be necessary (see Table 2).1 If serum phosphate with life-threatening consequences occurs and urgent intervention is required (e.g., dialysis), permanently discontinue erdafitinib therapy.1
Serum Phosphate Concentration (mg/dL) | Dosage Modification |
|---|---|
7-8.99 | Continue therapy at the current dosa start phosphate binder with food until phosphate level <7 mg/dL |
Reduce dose if phosphate level remains ≥7 mg/dL for a period of 2 months or if clinically necessary | |
9 to 10 | Withhold therapy with weekly reassessments until phosphate level <7 mg/dL; then restart at the same dose level |
Start phosphate binder with food until phosphate level <7 mg/dL | |
Reduce dose if phosphate level ≥9 mg/dL for a period of 1 month or if clinically necessary | |
>10 | Withhold therapy with weekly reassessments until phosphate level <7 mg/dL; then restart at the first reduced dose level |
If hyperphosphatemia (≥10 mg/dL) for >2 weeks, discontinue therapy permanently | |
Utilize medical management of symptoms as clinically relevant |
If central serous retinopathy occurs, temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of the drug as described in Table 3 may be necessary.1
Severity | Dosage Modification |
|---|---|
Any grade | Withhold erdafitinib and perform an ophthalmic evaluation within 2 weeks. If improving within 14 days, restart erdafitinib at the current dose If not improving within 14 days, withhold erdafitinib until improving; once improving, may resume at the next lower dose level Upon restarting erdafitinib, monitor for recurrence every 1 to 2 weeks for a month If recurs or has not improved after 4 weeks of withholding therapy, consider permanent discontinuation |
If other grade 3 adverse reactions occur, erdafitinib therapy should be withheld until the toxicity improves to grade 1 or baseline; therapy may then be resumed at a dosage reduced by 1 dose level.1
If grade 4 adverse reactions occur, erdafitinib therapy should be permanently discontinued.1
No dosage adjustment is necessary in patients with mild to moderate hepatic impairment (Child-Pugh class A or B).1
Limited data are available in patients with severe hepatic impairment (Child-Pugh class C).1
No dosage adjustment is necessary in patients with mild to moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-89 mL/minute per 1.73 m2).1
Limited data are available in patients with severe renal impairment.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Central serous retinopathy and retinal pigment epithelial detachment resulting in visual field defect have been reported in patients receiving erdafitinib.1 In the pooled safety population, central serous retinopathy/retinal pigment epithelial detachment occurred in 22% of erdafitinib-treated patients, with a median time to first onset of 46 days.1 In 104 patients with central serous retinopathy, 40% required dose interruptions and 56% required dose reductions; 2.9% required permanent treatment discontinuation.1 Of the 24 patients who restarted erdafitinib after dose interruption with or without dose reduction, 67% had recurrence and/or worsening of central serous retinopathy after reinitiation.1
Dry eye symptoms also have occurred in 26% of erdafitinib-treated patients.1 The manufacturer recommends prophylaxis with ocular demulcents as needed.1
Ophthalmologic examination, including visual acuity assessment, slit lamp examination, fundoscopy, and optical coherence tomography, should be performed monthly during the first 4 months of erdafitinib therapy; every 3 months thereafter; and as clinically indicated (e.g., if new or worsening visual disturbances occur).1 If visual symptoms are reported, ophthalmologic evaluations should be performed urgently.1 Temporary interruption or discontinuance of erdafitinib may be necessary if ocular toxicities occur during therapy with the drug.1
Hyperphosphatemia and Soft Tissue Mineralization
Increased serum phosphate concentration is a consequence of inhibition of fibroblast growth factor receptor (FGFR).1 Erdafitinib can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcinosis, nonuremic calciphylaxis, and vascular calcification.1 In the pooled safety population, hyperphosphatemia was reported in 73% of patients receiving erdafitinib.1 The median time to onset of increased phosphate was 16 days (range: 8-421 days) following initiation of erdafitinib.1 Twenty-four percent of patients received phosphate binders during erdafitinib therapy.1 Vascular calcification was seen in 0.2% of patients treated with erdafitinib.1
Because elevated phosphate concentrations occur frequently in patients receiving erdafitinib, phosphate intake should not exceed 600-800 mg daily during therapy and patients should avoid concurrent use of agents that may increase serum phosphate levels.1 If hyperphosphatemia (serum phosphate concentrations exceeding 7 mg/dL) occurs, an oral phosphate binder should be considered until serum phosphate concentrations improve to less than 7 mg/dL.1 Treatment interruption, dosage reduction, or permanent discontinuance of therapy may be necessary based on duration and severity of hyperphosphatemia.1
Fetal/Neonatal Morbidity and Mortality
Erdafitinib may cause fetal harm in humans based on its mechanism of action and animal findings; embryofetal toxicity and teratogenicity have been demonstrated in animals.1 There are no data regarding use of erdafitinib in pregnant women.1 In animal reproduction studies, embryofetal toxicity (i.e., death, decreased fetal body weight) and teratogenic effects (i.e., major blood vessel malformation and other vascular anomalies, limb malformation, skeletal anomalies) were observed in rats receiving erdafitinib at total maternal exposure levels less than 0.1% of total human exposure levels at the maximum recommended human dose.1
Pregnancy should be avoided during erdafitinib therapy.1 The manufacturer recommends confirmation of pregnancy status prior to initiation of erdafitinib in females of reproductive potential and states that such females should be advised to use effective contraceptive methods while receiving erdafitinib and for 1 month after discontinuance of the drug.1 In addition, males with such female partners should use effective methods of contraception while receiving erdafitinib and for 1 month after discontinuance of the drug.1 Patients should be apprised of the potential hazard to the fetus if erdafitinib is used during pregnancy.1
Erdafitinib may cause fetal harm if administered to pregnant females based on its mechanism of action and animal findings.1
It is not known whether erdafitinib is distributed into human milk.1 Because of the potential for serious adverse reactions to erdafitinib in breast-fed infants, females should be advised not to breast-feed while receiving the drug and for 1 month after the last dose.1 The effects of the drug on breast-fed infants or on the production of milk are unknown.1
Females and Males of Reproductive Potential
Females of reproductive potential should be advised to use effective contraceptive methods while receiving erdafitinib and for 1 month after discontinuance of the drug.1 In addition, males with such female partners should use effective methods of contraception while receiving erdafitinib and for 1 month after discontinuance of the drug.1
Based on animal studies, erdafitinib may impair female fertility.1 In a repeat-dose toxicity study, necrosis of ovarian corpora lutea was observed in female rats at exposure levels less than the human exposure at the maximum recommended human dosage.1
Safety and efficacy of erdafitinib have not been established in pediatric patients.1
Chondroid dysplasia or metaplasia in multiple bones and tooth abnormalities (i.e., abnormal or irregular dentin, odontoblast discoloration and degeneration) have been observed in animals receiving erdafitinib for 4 or 13 weeks (at exposure levels less than the AUC in humans at the maximum recommended dosage).1
In clinical trials, 40% of patients receiving erdafitinib were 65 to 74 years of age, while 20% were 75 years of age or older.1 Patients 65 years of age and older experienced a higher incidence of adverse reactions requiring treatment discontinuation than younger patients.1 No overall differences in efficacy were observed between geriatric patients and younger adults.1
Analysis of population pharmacokinetic data indicate that the pharmacokinetics of erdafitinib are not substantially altered in patients with mild or moderate hepatic impairment (Child-Pugh class A or B).1, 3
Limited data are available in patients with severe hepatic impairment (Child-Pugh class C).1
Analysis of population pharmacokinetic data indicate that the pharmacokinetics of erdafitinib are not substantially altered in patients with mild or moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-89 mL/min per 1.73 m2).1, 3
Pharmacokinetics of erdafitinib have not been established in patients with severe renal impairment or renal impairment requiring dialysis.1
Pharmacogenomic Considerations
Patients who are known or suspected poor cytochrome P-450 (CYP) isoenzyme 2C9 metabolizers carrying the CYP2C9*3/*3 genotype should be monitored for adverse effects since systemic exposure to the drug may be increased.1, 3
Adverse effects and laboratory abnormalities reported in at least 20% of patients receiving erdafitinib include increased phosphate, nail disorders, stomatitis, diarrhea, increased creatinine, increased alkaline phosphatase, increased ALT, decreased hemoglobin, decreased sodium, increased AST, fatigue, dry mouth, dry skin, decreased phosphate, decreased appetite, dysgeusia, constipation, increased calcium, dry eye, palmar-plantar erythrodysesthesia syndrome, increased potassium, alopecia, and central serous retinopathy.1
Erdafitinib is metabolized principally by cytochrome P-450 (CYP) isoenzymes 2C9 and 3A4.1 In vitro, erdafitinib demonstrates time-dependent inhibition and induction of CYP3A4.1 In vitro, the drug is not an inhibitor of other major CYP isoenzymes at clinically relevant concentrations.1
In vitro studies indicate that erdafitinib is a substrate of P-glycoprotein (P-gp).1 In vitro, erdafitinib is an inhibitor of P-gp and organic cation transporter (OCT) 2, but does not inhibit breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B or 1B3, organic anion transporter (OAT) 1 or 3, OCT1, and multidrug and toxin extrusion (MATE) 1 or 2K transporters at clinically important concentrations.1
Drugs Affecting Hepatic Microsomal Enzymes
Inhibitors of CYP2C9 and/or 3A4
Concomitant use of erdafitinib with moderate inhibitors of CYP2C9 or strong inhibitors of 3A4 may result in increased erdafitinib plasma concentrations and increased risk of erdafitinib toxicity.1 When the strong CYP2C9 and moderate CYP3A4 inhibitor fluconazole (400 mg daily on days 1-11) was administered concomitantly with erdafitinib (single 4-mg dose on day 5) in healthy individuals, peak plasma concentrations and AUC of erdafitinib were increased by 21 and 48%, respectively.1, 3 When the strong CYP3A4 inhibitor and P-gp inhibitor itraconazole (200 mg daily on days 1-11) was administered concomitantly with erdafitinib (single 4-mg dose on day 5) in healthy individuals, peak plasma concentrations and AUC of erdafitinib were increased by 5 and 34%, respectively.1, 3
Concomitant use of erdafitinib with moderate inhibitors of CYP2C9 and strong inhibitors of CYP3A4 (e.g., fluconazole, itraconazole) should be avoided, and selection of an alternative drug with less CYP2C9 or 3A4 inhibition potential should be considered.1 If concomitant use of a moderate CYP2C9 or strong CYP3A4 inhibitor cannot be avoided, patients should be monitored closely for signs of erdafitinib toxicity and a dose modification considered.1 When concomitant use of the moderate CYP2C9 or strong CYP3A4 inhibitor is discontinued, resume the erdafitinib dose used before dose modifications in the absence of drug-related toxicity.1
Concomitant use of erdafitinib with strong or moderate inducers of CYP3A4 may result in decreased erdafitinib plasma concentrations and reduced erdafitinib efficacy.1 Simulations suggest that peak plasma concentrations and AUC of erdafitinib are substantially decreased following concomitant administration of the drug with the strong CYP3A4 inducer rifampin.1
Concomitant use of erdafitinib with strong (e.g., rifampin) inducers of CYP3A4 should be avoided.1, 3 If concomitant use of a moderate 3A4 inducer cannot be avoided upon initiation of erdafitinib, the manufacturer states that erdafitinib should be initiated at 9 mg once daily.1 When concomitant use of the moderate CYP3A4 inducer is discontinued, the erdafitinib dosage should be continued at the same dosage, in the absence of drug-related toxicity.1
Drugs Metabolized by Hepatic Microsomal Enzymes
Because erdafitinib is a time-dependent inhibitor and inducer of CYP3A4, concomitant use of erdafitinib with drugs that are substrates of CYP3A4 may result in altered plasma concentrations of the CYP3A4 substrate and either reduced efficacy or increased toxicity of the CYP3A4 substrate; however, the effect of erdafitinib on sensitive CYP3A4 substrates (e.g., midazolam) has not been established.1, 3
Concomitant use of erdafitinib with sensitive CYP3A4 substrates that have a narrow therapeutic index should be avoided.1
Drugs Affecting or Affected by P-glycoprotein Transport
Concomitant use of erdafitinib and inhibitors of P-gp are not expected to have a clinically important effect on systemic exposure of erdafitinib.1
Concomitant use of erdafitinib with drugs that are substrates of P-gp may result in increased exposure of the P-gp substrate and increased risk of toxicity of the P-gp substrate.1 If concomitant use is necessary, erdafitinib should be administered at least 6 hours before or after administration of P-gp substrates that have a narrow therapeutic index (e.g., digoxin).1, 3
Drugs Affecting Serum Phosphate Concentrations
Concomitant use of erdafitinib with other drugs that alter serum phosphate concentrations may result in increased or decreased serum phosphate concentrations.1
In clinical trials, concomitant use of erdafitinib with other drugs that increase serum phosphate concentrations (e.g., potassium phosphate supplements, vitamin D supplements, antacids, phosphate-containing laxatives, and medications containing phosphate as an excipient) were not permitted.1 Because the initial dosage titration of erdafitinib is based on serum phosphate concentrations, concomitant use of erdafitinib with other drugs that may alter serum phosphate concentrations should be avoided during the initial dosage titration period (i.e., initial 14-21 days of erdafitinib therapy).1
Concomitant administration of erdafitinib with drugs that reduce gastric acidity such as antacids, histamine H2-receptor antagonists, and proton-pump inhibitors do not have a clinically meaningful effect on bioavailability of erdafitinib.1
Erdafitinib, a potent and reversible inhibitor of fibroblast growth factor receptors (FGFR)-1, FGFR-2, FGFR-3, and FGFR-4, is an antineoplastic agent.1, 2, 5, 8 Similar to other receptor tyrosine kinases, activation of FGFR tyrosine kinase is involved in the initiation of various cascades of intracellular signaling events leading to cell proliferation and influences processes critical to cell survival and tumor progression (e.g., angiogenesis, metastasis, inhibition of apoptosis).5, 6 Aberrations in FGFR (e.g., gene amplification, point mutation, chromosomal translocation) resulting in dysregulation of the FGFR signaling cascade have been implicated in various solid tumors;5, 6 the reversible binding of erdafitinib to and subsequent inhibition of FGFR-1, FGFR-2, FGFR-3, and FGFR-4 reduces cell viability in cell lines expressing aberrant FGFR.1, 5 The drug also has demonstrated antitumor activity in FGFR-expressing cell lines and xenograft models of tumor types such as bladder cancer.1 Erdafitinib also has demonstrated binding to ret proto-oncogene (RET), colony stimulating factor receptor type 1 (CSF-1R), platelet-derived growth factor receptors (PDGFR)-α and PDGFR-β, fms-like tyrosine kinase-4 (Flt-4), stem cell factor receptor (c-Kit), and vascular endothelial growth factor receptor (VEGFR)-2.1, 3, 8
Serum phosphate concentration is a marker of FGFR inhibition following initiation of erdafitinib therapy.3 In an exposure-response analysis, a significant relationship between better investigator-assessed clinical outcomes (i.e., objective response rate, disease control rate, progression-free survival) and increased serum phosphate concentrations was observed.3
Peak plasma concentrations and AUC of erdafitinib are dose proportional over the erdafitinib dose range of 0.5-12 mg following single or repeated once-daily dosing.1, 6 The median time to peak plasma concentration of erdafitinib is 2.5 hours.1, 6 Steady-state concentrations of erdafitinib are reached after 2 weeks of once-daily dosing and the accumulation ratio is approximately 4-fold.1 Administration of a single 9-mg dose of erdafitinib with a high-fat, high-calorie meal (800-1000 calories with approximately 50% of calories from fat) in healthy individuals did not have a clinically meaningful effect on the pharmacokinetics of erdafitinib.1, 3
Erdafitinib is metabolized principally by cytochrome P-450 (CYP) isoenzymes 2C9 and 3A4.1 Erdafitinib is highly bound (99.8%) to plasma proteins in vivo, primarily to α1-acid glycoprotein.1 The mean effective half-life of erdafitinib is 59 hours.1 Following administration of a single oral radiolabeled dose of erdafitinib, 69% of the recovered dose is excreted in feces (19% as unchanged drug) and 19% is eliminated in urine (13% as unchanged drug).1 Clearance of erdafitinib does not appear to be affected by age (range: 21-88 years), sex, race, or body weight (range: 36-132 kg).1, 3
Genetic polymorphism of the CYP2C9 isoenzyme may affect exposure to erdafitinib.1 Systemic exposure of erdafitinib was similar in patients with CYP2C9*1/*2 and CYP2C9*1/*3 genotypes compared with individuals with the CYP2C9*1/*1 wild-type genotype.1 Erdafitinib has not been studied in individuals with other CYP2C9 genotypes (e.g., CYP2C9*2/*2, CYP2C9*2/*3, CYP2C9*3/*3); however, pharmacokinetic modeling suggests that no clinically meaningful changes in systemic exposure of erdafitinib are expected in individuals with CYP2C9*2/*2 and CYP2C9*2/*3 genotypes.1, 3 Pharmacokinetic modeling also suggests that systemic exposure of erdafitinib is expected to increase by 50% in individuals with the CYP2C9*3/*3 genotype compared with individuals with the CYP2C9*1/*1 wild-type genotype.1, 3
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Erdafitinib is available only from a designated specialty pharmacy.7 The manufacturer should be contacted for additional information.7
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions December 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Janssen. Balversa® (erdafitinib) tablets prescribing information. Horsham, PA; 2024 Oct.
2. Loriot Y, Necchi A, Park SH et al. Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma. N Engl J Med . 2019; 381:338-348. [PubMed 31340094]
3. Food and Drug Administration. Center for Drug Evaluation and Research. Application number: 212018Orig1s000: Multi-discipline review. From FDA website. [Web]
5. Dai S, Zhou Z, Chen Z et al. Fibroblast Growth Factor Receptors (FGFRs): Structures and Small Molecule Inhibitors. Cells . 2019; 8 [PubMed 31216761]
6. Nishina T, Takahashi S, Iwasawa R et al. Safety, pharmacokinetic, and pharmacodynamics of erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, in patients with advanced or refractory solid tumors. Invest New Drugs . 2018; 36:424-434. [PubMed 28965185]
7. Janssen Biotech, Inc. From Balversa® (erdafitinib) for healthcare professionals website. Accessed 2024 May 6. [Web]
8. Perera TPS, Jovcheva E, Mevellec L et al. Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor. Mol Cancer Ther . 2017; 16:1010-1020. [PubMed 28341788]
9. Siefker-Radtke AO, Necchi A, Park SH et al. Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study. Lancet Oncol . 2022; 23:248-258. [PubMed 35030333]
15. Loriot Y, Matsubara N, Park S H, et al. Erdafitinib or chemotherapy in advanced or metastatic urothelial carcinoma. N Engl J Med . 2023;389:1961-71.
16. Siefker-Radtke AO, Matsubara N, Park SH, et al. Erdafitinib versus pembrolizumab in pretreated patients with advanced or metastatic urothelial cancer with select FGFR alterations: cohort 2 of the randomized phase III THOR trial. Ann Oncol . 2024;35(1):107-117.
17. Powles T, Bellmunt J, Comperat E. et al. on behalf of the ESMO Guidelines Committee. ESMO clinical practice guideline interim update on first-line therapy in advanced urothelial carcinoma. Ann Oncol . 2024.