OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Erdafitinib – Balversa®

DRUG CLASS

Antineoplastic Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Erdafitinib	1346242-81-6	C25-H30-N6-O2

ANNOTATED BIBLIOGRAPHY

References updated: 01 December 2022

Abbreviations: FGF, fibroblast growth factor.

• Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.

  (Review of hepatotoxicity published in 1999 before the availability of tyrosine kinase receptor inhibitors).
• DeLeve LD. Kinase inhibitors. Cancer chemotherapy. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, p. 556.

  (Review of hepatotoxicity of cancer chemotherapeutic agents, does not discuss erdafitinib).
• Wellstein A, Giaccone G, Atkins MB, Sausville EA. Pathway targeted therapies: monoclonal antibodies, protein kinase inhibitors, and various small molecules. In, Brunton LL Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 1203-36.

  (Textbook of pharmacology and therapeutics).
• FDA. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2019/212018Orig1s000MultidisciplineR.pdf.

  (FDA website with product labels and initial clinical review of the safety and efficacy of erdafitinib; states that virtually all patients had at least one adverse event and that serious adverse events arose in 67 of 164 patients [41%],most commonly hyperphosphatemia [82%], stomatitis [56%], creatinine elevations [49%], dry mouth [46%], alkaline phosphatase elevations [44%], diarrhea [42%), and ALT elevations [42%, which were above 5 times ULN in 2%], but there were no instances of aminotransferase elevations with jaundice).
• Arai Y, Totoki Y, Hosoda F, Shirota T, Hama N, Nakamura H, Ojima H, et al. Fibroblast growth factor receptor tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma. Hepatology. 2014;59:1427–34. [PubMed: 24122810]

  (Whole transcriptome sequencing from 8 cholangiocarcinomas identified two FGF receptor fusion genes and screening of different human cancer tissues found FGF receptor fusions in 9 of 102 cholangiocarcinomas [all intrahepatic] but only 1 of 149 colorectal, 1 of 96 hepatocellular, and none of 212 gastric cancers; expression of the fusion kinases in cell cultures led to anchorage independent growth and tumorigenesis when implanted in mice).
• Karkera JD, Cardona GM, Bell K, Gaffney D, Portale JC, Santiago-Walker A, Moy CH, 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;16:1717–1726. [PubMed: 28416604]

  (Analysis of cancer cell lines and tumor tissue from patients found that gene alterations in FGF receptors [translocations, gene amplification, point mutations] were associated with increased pathway activation and with responsivity to erdafitinib inhibition, suggesting that the FGF pathway would be a potential target for inhibition).
• Markham A. Erdafitinib: first global approval. Drugs. 2019;79:1017–1021. [PubMed: 31161538]

  (Review of the mechanism of action, history of development, pharmacology, clinical efficacy and safety of erdafitinib shortly after its approval for use in the US as therapy of urothelial carcinoma with FGF receptor 2 or 3 mutations that adverse events occur in most patients and severe events arise in 41% of patients and account for discontinuation in 13% and drug interruptions in 68% of recipients; mentions but does not specifically discussion ALT elevations).
• Loriot Y, Necchi A, Park SH, Garcia-Donas J, Huddart R, Burgess E, Fleming M, et al. BLC2001 Study Group. Erdafitinib in locally advanced or metastatic urothelial carcinoma. N Engl J Med. 2019;381:338–348. [PubMed: 31340094]

  (Among 99 patients with advanced or metastatic urothelial carcinoma enrolled in an open label trial of erdafitinib [8 mg daily], the confirmed response rate was 40% [complete 3%], and the progression free survival 6.5 months, while adverse events occurred in all patients and included hyperphosphatemia [77%], stomatitis [58%], diarrhea [51%], dry mouth [46%], decreased appetite [37%], dry skin [32%], alopecia [29%], constipation [28%], asthenia [20%], ALT elevations [17%, 2% above 5 times ULN], but there was no clinically apparent liver injury with jaundice).
• Schlotman A, Stater A, Schuler K, Heideman J, Abramson V. Grade 3 hepatotoxicity following fulvestrant, palbociclib, and erdafitinib therapy in a patient with ER-positive/PR-negative/HER2-negative metastatic breast cancer: a case report. Case Rep Oncol. 2020;13:304–308. [PMC free article: PMC7154258] [PubMed: 32308596]

  (49 year old woman with breast cancer developed fatigue after 2 days of combination chemotherapy with erdafitinib, palbociclib and fulvestrant followed by diarrhea and abdominal pain, and laboratory tests at week one showed [ALT 522 U/L, Alk P 281 U/L, bilirubin 0.9 mg/dL] that rapidly fell to normal upon stopping all 3 agents).
• Krook MA, Reeser JW, Ernst G, Barker H, Wilberding M, Li G, Chen HZ, et al. Fibroblast growth factor receptors in cancer: genetic alterations, diagnostics, therapeutic targets and mechanisms of resistance. Br J Cancer. 2021;124:880–892. [PMC free article: PMC7921129] [PubMed: 33268819]

  (Review of the FGF receptors and their gene alterations in cancers including translocations, rearrangements, fusions, increase in copy numbers, and point mutations which are found in 5-10% of cancers, most frequently in urothelial cancers and cholangiocarcinoma [10-30%]; targeted therapy using inhibitors of FGF receptors has been limited by the development of resistance in many patients).