BALVERSA® (erdafitinib) HCP

Genetic alterations in FGFR are believed to influence urothelial carcinoma cell growth and proliferation^1-3

Recent interest in the development of targeted therapies for advanced urothelial carcinoma is validated by data establishing that these cancers can harbor genetic alterations. Some of the most common alterations occur in the FGFR genes, particularly FGFR3.^4-6

FGFR genetic alterations may cause constitutive signaling^2,3

The interaction of altered F G F R on intracellular signaling pathways in a Urothelial Cancer Cell

Five blue human icons and one has a green double helix under it. About one in five patients with M I B C has F G F R alterations

Test for FGFR alterations to identify patients who may be eligible for BALVERSA^®

Learn more about an FDA-approved companion diagnostic test at QIAGEN.com

An FDA-approved companion diagnostic test helps identify patients whose tumors have certain FGFR genetic alterations.⁸ The test detects certain clinically actionable FGFR genetic alterations from formalin-fixed paraffin-embedded urothelial tumor tissue.⁹

The approved companion diagnostic is available in various national and regional molecular pathology testing labs.

Find a testing lab located near you

FDA = U.S. Food and Drug Administration; FGF = fibroblast growth factor; FGFR = fibroblast growth factor receptor; MIBC = muscle-invasive bladder cancer.

References

1. di Martino E, Tomlinson DC, Williams SV, Knowles MA. A place for precision medicine in bladder cancer: targeting the FGFRs. Future Oncol. 2016;12(19):2243-2263. 2. 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(6):1010-1020. 3. Karkera JD, Cardona GM, Bell K, et al. Oncogenic characterization and pharmacologic sensitivity of activating fibroblast growth factor receptor (FGFR) genetic alterations to the selective FGFR inhibitor erdaﬁtinib. Mol Cancer Ther. 2017;16(8):1717-1726. 4. Ross JS, Wang K, Al-Rohil RN, et al. Advanced urothelial carcinoma: next-generation sequencing reveals diverse genomic alterations and targets of therapy. Modern Pathol. 2014;27(2):271-280. 5. Ross JS, Wang K, Khaira D, et al. Comprehensive genomic profiling of 295 cases of clinically advanced urothelial carcinoma of the urinary bladder reveals a high frequency of clinically relevant genomic alterations. Cancer. 2016;122(5):702-711. 6. Helsten T, Elkin S, Arthur E, et al. The FGFR landscape in cancer: analysis of 4,853 tumors by next-generation sequencing. Clin Cancer Res. 2015;22(1):259-267. 7. Tomlinson DC, Baldo O, Harnden P, et al. FGFR3 protein expression and its relationship to mutation status and prognostic variables in bladder cancer. J Pathol. 2007;213(1):91-98. 8. US Food and Drug Administration. List of cleared or approved companion diagnostic devices (in vitro and imaging tools). Accessed January 17, 2023. https://www.fda.gov/medical-devices/vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-vitro-and-imaging-tools 9. therascreen® FGFR RGQ RT-PCR Kit, Instructions for Use (Handbook). HB-2561-001, version 1, April 2019. Germantown, MD: QIAGEN N.V.

Warnings and Precautions

Ocular Disorders — BALVERSA^® can cause ocular disorders, including central serous retinopathy/retinal pigment epithelial detachment (CSR/RPED) resulting in visual field defect.

CSR/RPED was reported in 25% of patients treated with BALVERSA^®, with a median time to first onset of 50 days. Grade 3 CSR/RPED, involving central field of vision, was reported in 3% of patients. CSR/RPED resolved in 13% of patients and was ongoing in 13% of patients at the study cutoff. CSR/RPED led to dose interruptions and reductions in 9% and 14% of patients, respectively, and 3% of patients discontinued BALVERSA^®. Dry eye symptoms occurred in 28% of patients during treatment with BALVERSA^® and were Grade 3 in 6% of patients. All patients should receive dry eye prophylaxis with ocular demulcents as needed.

Perform monthly ophthalmological examinations during the first 4 months of treatment and every 3 months afterwards, and urgently at any time for visual symptoms. Ophthalmological examination should include assessment of visual acuity, slit lamp examination, fundoscopy, and optical coherence tomography. Withhold BALVERSA^® when CSR occurs and permanently discontinue if it does not resolve within 4 weeks or if Grade 4 in severity. For ocular adverse reactions, follow the dose modification guidelines [see Dosage and Administration (2.3)].

Hyperphosphatemia and Soft Tissue Mineralization — BALVERSA^® can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcinosis, non-uremic calciphylaxis and vascular calcification. Increases in phosphate levels are a pharmacodynamic effect of BALVERSA^® [see Pharmacodynamics (12.2)]. Hyperphosphatemia was reported as adverse reaction in 76% of patients treated with BALVERSA^®. The median onset time for any grade event of hyperphosphatemia was 20 days (range: 8–116) after initiating BALVERSA^®. Thirty-two percent of patients received phosphate binders during treatment with BALVERSA^®. Cutaneous calcinosis, non-uremic calciphylaxis and vascular calcification have been observed in 0.3% of patients treated with BALVERSA^®.

Monitor for hyperphosphatemia throughout treatment. In all patients, restrict phosphate intake to 600‑800 mg daily. If serum phosphate is above 7.0 mg/dL, consider adding an oral phosphate binder until serum phosphate level returns to <5.5 mg/dL. Withhold, dose reduce, or permanently discontinue BALVERSA^® based on duration and severity of hyperphosphatemia [see Dosage and Administration (2.3), Table 2: Dose Modifications for Adverse Reactions].

Embryo-Fetal Toxicity — Based on the mechanism of action and findings in animal reproduction studies, BALVERSA^® can cause fetal harm when administered to a pregnant woman. In a rat embryo-fetal toxicity study, erdafitinib was embryotoxic and teratogenic at exposures less than the human exposures at all doses studied. Advise pregnant women of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with BALVERSA^® and for one month after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with BALVERSA^® and for one month after the last dose [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1)].

Most common adverse reactions including laboratory abnormalities ≥20%:

Phosphate increased (76%), stomatitis (56%), fatigue (54%), creatinine increased (52%), diarrhea (47%), dry mouth (45%), nail disorder (45%), 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%), alopecia (26%), palmar-plantar erythrodysesthesia syndrome (26%), constipation (28%), phosphate decreased (24%), abdominal pain (23%), calcium increased (22%), nausea (21%), and musculoskeletal pain (20%). The most common Grade 3 or greater adverse reactions (>1%) were stomatitis (9%), nail dystrophy*, palmar-plantar erythrodysesthesia syndrome (6%), paronychia (3%), nail disorder (10%), keratitis^†, and hyperphosphatemia (1%).

*Included within nail disorder. ^†Included within dry eye.

An adverse reaction with a fatal outcome in 1% of patients was acute myocardial infarction.
Serious adverse reactions occurred in 41% of patients, including eye disorders (10%).
Permanent discontinuation due to an adverse reaction occurred in 13% of patients. The most frequent reasons for permanent discontinuation included eye disorders (6%).
Dosage interruptions occurred in 68% of patients. The most frequent adverse reactions requiring dosage interruption included hyperphosphatemia (24%), stomatitis (17%), eye disorders (17%), and palmar-plantar erythrodysesthesia syndrome (8%).
Dose reductions occurred in 53% of patients. The most frequent adverse reactions for dose reductions included eye disorders (23%), stomatitis (15%), hyperphosphatemia (7%), palmar-plantar erythrodysesthesia syndrome (7%), paronychia (7%), and nail dystrophy (6%).

Drug Interactions

Moderate CYP2C9 or strong CYP3A4 inhibitors: Consider alternative agents or monitor closely for adverse reactions. (7.1)
Strong CYP2C9 or CYP3A4 inducers: Avoid concomitant use with BALVERSA^®. (7.1)
Moderate CYP2C9 or CYP3A4 inducers: Increase BALVERSA^® dose up to 9 mg. (7.1)
Serum phosphate level-altering agents: Avoid concomitant use with agents that can alter serum phosphate levels before the initial dose modification period. (2.3, 7.1)
CYP3A4 substrates: Avoid concomitant use with sensitive CYP3A4 substrates with narrow therapeutic indices. (7.2)
OCT2 substrates: Consider alternative agents or consider reducing the dose of OCT2 substrates based on tolerability. (7.2)
P-gp substrates: Separate BALVERSA^® administration by at least 6 hours before or after administration of P-gp substrates with narrow therapeutic indices. (7.2)

Use in Specific Populations

Lactation — Because of the potential for serious adverse reactions from erdafitinib in a breastfed child, advise lactating women not to breastfeed during treatment with BALVERSA^® and for one month following the last dose.

Please click here to see full BALVERSA^® Prescribing Information.

cp-69605v6

FGFR and Biomarker Testing

Genetic alterations in FGFR are believed to influence urothelial carcinoma cell growth and proliferation^1-3

FGFR genetic alterations may cause constitutive signaling^2,3

Test for FGFR alterations to identify patients who may be eligible for BALVERSA^®

STUDY DESIGN

MECHANISM OF ACTION

SAFETY

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FGFR and Biomarker Testing

Genetic alterations in FGFR are believed to influence urothelial carcinoma cell growth and proliferation1-3

FGFR genetic alterations may cause constitutive signaling2,3

Test for FGFR alterations to identify patients who may be eligible for BALVERSA®

STUDY DESIGN

MECHANISM OF ACTION

SAFETY

You are leaving the BALVERSA® (erdafitinib) HCP website.

For Healthcare Professionals

Genetic alterations in FGFR are believed to influence urothelial carcinoma cell growth and proliferation^1-3

FGFR genetic alterations may cause constitutive signaling^2,3

Test for FGFR alterations to identify patients who may be eligible for BALVERSA^®

You are leaving the BALVERSA^® (erdafitinib) HCP website.