RX Road Map: Erdafitinib (Balversa)

Who Is This Drug Approved For

Erdafitinib is approved for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) with associated fibroblast growth factor receptor (FGFR) 3 genetic alterations having progressed on or after at least 1 line of prior systemic therapy.Erdafitinib is not recommended for treatment of patients who are eligible for PD1 or PD-L1 inhibitor therapy and have not yet received this line of therapy.

RX Road Map: Erdafitinib (Balversa)

Pivotal Clinical Trials Supporting Approval:

• BCL2001 (NCT02365597): Phase 2, multicenter, open label, single arm study to evaluate the efficacy and safety of erdafitinib in 87 patients with locally advanced or mUC who had progressed on at least 1 line of prior platinum-based chemotherapy and with tumors with at least 1 FGFR mutation.Objective response rate (ORR) 32.2% and included patients who had previously not responded to anti PDL1-PD1 therapy.Median duration of response (DoR) 5.4 months.
• BLC3001 (THOR) Cohort 1: Randomized, open label, multicenter, Phase 3 study of erdafitinib vs. chemotherapy in 266 patients with mUC with FGFR 3 alterations who had progression after 1 or 2 previous lines of therapy that included an anti PD1 or anti PDL1 agent.Patients randomly assigned 1:1 to receive erdafitinib or investigators choice of chemotherapy (docetaxel or venflunine).Primary endpoint was overall survival (OS). OS (12.1 months versus 7.8 months), progression-free survival (PFS) (5.6 months versus 2.7 months) and overall response rate (ORR) (35.3% versus 8.5%) improved in the erdafitinib arm.
• BLC3001 (THOR) Cohort 2:Multicenter, open label, randomized study of 351 patients with locally advanced or mUC with FGFR3 alterations having received 1 prior line of systemic therapy and no prior PD1 or PD-L1 inhibitor.Patients randomized 1:1 to receive erdafitinib or pembrolizumab.Did not meet primary endpoint of OS superiority (median 10.9 months for erdafitinib verses 11.1 months for pembrolizumab).

MECHANISM OF ACTION: Oral kinase inhibitor of FGFR.FGFR gene alterations are involved in the deregulation of proliferation of certain tumor cells.

DOSING INFORMATION:Recommended initial dosage of 8 mg orally once daily with a dose increase to 9 mg daily based on tolerability and hyperphosphatemia.At days 14-21 after initiating treatment, serum phosphate level should be assessed, and the dose should be increased to 9 mg if serum phosphate level is less than 9.0 mg/dL and there are no ocular disorders or grade >2 adverse events.

ADMINISTRATION: Erdafitinib is available in 3, 4, and 5mg tablets. Tablets should be swallowed whole with or without food.

RECOMMENDED DURATION OF THERAPY:Treatment with erdafitinib should continue until disease progression or unacceptable toxicity.

WARNINGS AND PRECAUTIONS:

• Ocular events:Erdafitinib can cause central serous retinopathy/retinal pigment epithelial detachment (CSR/RPED).Baseline and monthly ophthalmologic evaluations should be done during the first 4 months of treatment then Q 3 months or with any visual changes.Erdafitinib should be withheld if CSR/RPED occurs and permanently discontinued without resolution within 4 weeks or if grade 4 severity.
• Hyperphosphatemia:Elevated phosphate levels are an expected on target effect of erdafitinib.Monitoring phosphate levels and management with the appropriate dose modifications required.
• Embryo fetal toxicity:Use of erdafitinib can cause fetal harm.Patients should be instructed to use effective contraception.Patients should not breastfeed while taking erdafitinib.

ADVERSE REACTIONS/MANAGEMENT:

• The most common (20%) adverse reactions associated with erdafitinib included: Increased phosphate, nail disorders, stomatitis, diarrhea, increased creatinine, increased alkaline phosphatase (ALP), increased alanine aminotransferase (ALT), decreased hemoglobin, decreased sodium, increased aspartate aminotransferase (AST), fatigue, dry mouth, dry skin, decreased phosphate, decreased appetite, taste changes, constipation, increased calcium, dry eye, palmar-plantar erythrodysesthesia syndrome, increased potassium, alopecia and central serous retinopathy.
• Hyperphosphatemia: IN ALL PATIENTS RESTRICT PHOSPHATE INTAKE TO 600-800MG/DAY
• CSR:With hold erdafitinib and obtain ophthalmic evaluation within 2 weeks.Erdafitinib can be restarted if improving within 14 days at the current dose, otherwise withhold until improved and then resume at the next lower dose level.Patient should be monitored every 1-2 weeks for a month after development of CSR.If recurs or has not improved after 4 weeks of withholding erdafitinib consider permanent discontinuation.
• For other adverse events (AE), erdafitinib should be held for grade 3 AEs, until resolves to grade 1 and then can resume with dose reduction. Permanently discontinue for any grade 4 AE.

ESSENTIAL PATIENT INFORMATION:

• Confirmation of the presence of FGFR3 genetic alteration in tumor specimens must be completed prior to initiation of treatment with erdafitinib.Information on FDA approved test for detection of FGFR 3 genetic alterations in urothelial cancers available at http://www.fda.gov/CompanionDiagnostics.
• Notify oncology care team with any visual changes. In order to prevent or treat dry eyes, use of artificial tears substitutes, hydrating or lubricating eye gels or ointments, should be used at least every 2 hours while awake.
• Notify oncology care team with any progressive skin, mucous or nail changes.
• All patients should be advised that erdafitinib can cause hyperphosphatemia and to contact oncology care team with any changes that may be associated with acute hyperphosphatemia including muscle cramps, numbness or tingling around the mouth.
• All patients should restrict phosphate intake to 600-800 mg daily.
• Female patients of childbearing potential should receive a pregnancy test prior to initiation of erdafitinib and instructed to use effective birth control during and for one month after discontinuation of erdafitinib. Male patients with female partners that may become pregnant should also use effective birth control during and for one month after the last dose of erdafitinib.
• Inform oncology care team immediately if you become pregnant or think you may be pregnant.
• Do not breastfeed during treatment or for one month after completion of erdafitinib.

NURSING CONSIDERATIONS (CONCOMITANT FOOD/DRUG INTERACTIONS AND MONITORING):

• If dose is missed it can be taken as soon as possible on the same day, resuming daily dosing schedule the following day.If vomiting occurs, extra tablets should not be taken to make up for missed or lost dose.
• Concomitant use of strong CYP34A inducers should be avoided; moderate CYP34A inducers should be given with erdafitinib at dose of 9 mg daily.
• Consider alternate medications or monitor closely for adverse side effects when used with moderate CYP2C9 or strong CYP34 A inhibitors.
• P-GP substrates should be separated by at least 6 hours before or after administration of erdafitinib.

SAFE HANDLING INSTRUCTIONS: Store at room temperature and keep out of reach of children.

REFERENCES:

BALVERSA Prescribing Information.Janssen Pharmaceutical Companies; 2019.Accessed July 17, 2024 https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/BALVERSA-pi.pdf

Loriot Y, Matsubara N, Park SH, et al.Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma, N Engl J Med 2023;389:1961-1971. DOI: 10.1056/NEJMoa2308849