OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Pemigatinib – Pemazyre®

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
Pemigatinib	1513857-77-6	C24-H27-F2-N5-O4

ANNOTATED BIBLIOGRAPHY

References updated: 30 November 2022

Abbreviations: FGF, fibroblast growth factor.

• Zimmerman HJ. 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 small molecule FGF receptor inhibitors).
• DeLeve LD. Erlotinib. Cancer chemotherapy. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 556.

  (Review of hepatotoxicity of cancer chemotherapeutic agents discusses several tyrosine kinase inhibitors including imatinib, gefitinib, erlotinib and crizotinib, but not pemigatinib).
• 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/2020/213736Orig1s000MultidisciplineR.pdf.

  (FDA website with product labels, letters and multidisciplinary review of the applications for pemigatinib mentions that adverse events were common, led to drug discontinuation in 9%, interruptions in 43% [some due to ALT elevations], dose reductions in 14%, and ALT elevations in 43-50% of treated subjects which were above 5 times ULN in 4-12%, but all were self-limited and there were no drug related serious hepatic adverse events or instances of clinically apparent liver injury with jaundice).
• Shah RR, Morganroth J, Shah DR. Hepatotoxicity of tyrosine kinase inhibitors: clinical and regulatory perspectives. Drug Saf. 2013;36:491–503. [PubMed: 23620168]

  (Review of the hepatotoxicity of 18 tyrosine kinase inhibitors approved for use in cancer in the US as of 2013, before the availability of pemigatinib).
• 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).
• Pemigatinib (Pemazyre) for cholangiocarcinoma. Med Lett Drugs Ther. 2018;60(1546):e208–e209. [PubMed: 33451178]

  (Concise review of the mechanism of action, pharmacokinetics, clinically efficacy, safety and costs of pemigatinib shortly after it was approved for use in cholangiocarcinoma, adverse events being common but no mention of hepatotoxicity or serum ALT elevations).
• Liu PCC, Koblish H, Wu L, Bowman K, Diamond S, DiMatteo D, Zhang Y, et al. INCB054828 (pemigatinib), a potent and selective inhibitor of fibroblast growth factor receptors 1, 2, and 3, displays activity against genetically defined tumor models. PLoS One. 2020;15:e0231877. [PMC free article: PMC7313537] [PubMed: 32315352]

  (Review of the FGF cell pathway, effects of inhibiting the FGF receptor and the implications of such inhibition for cancer chemotherapy).
• Abou-Alfa GK, Sahai V, Hollebecque A, Vaccaro G, Melisi D, Al-Rajabi R, Paulson AS, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020;21:671–684. [PMC free article: PMC8461541] [PubMed: 32203698]

  (Among 146 adults with locally advanced or metastatic cholangiocarcinoma treated with pemigatinib, objective responses arose in 36% of patients with FGF receptors aberrations but in none of those without, adverse events were common and included hyperphosphatemia [55%], nausea, fatigue and nail changes; ALT elevations arose in only 2% of treated patients).
• Hoy SM. Pemigatinib: first approval. Drugs. 2020;80:923–929. [PubMed: 32472305]

  (Review of the chemical structure, mechanism of action, clinical efficacy and costs of pemigatinib which is a specific inhibitor of FGF receptors 1, 2 and 3, but also has activity against other targets perhaps accounting for some of its adverse effects).
• 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 association of FGF receptors and cancer chemotherapeutic agents, activating mutations being found in 5-10% of cancers overall, but in 10-20% of cholangiocarcinomas).
• Yang X, Yang X, Zhao H. Pemigatinib-related calcification in the liver. Am J Gastroenterol. 2022 Nov 4; Epub ahead of print. [PubMed: 36191267]

  (54 year old man with refractory cholangiocarcinoma achieved a remission after 3 months of treatment with pemigatinib, but 8 months later was found to have calcifications in the liver around the tumor 8, probably the result of hyperphosphatemia).