Gap between pediatric and adult approvals of molecular targeted drugs.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Antineoplastic Agents/*therapeutic use ; Drug Approval/*legislation & jurisprudence ; Neoplasms/*drug therapy; Adult ; Child ; European Union ; Humans ; Japan ; Molecular Targeted Therapy/methods ; United States ; United States Food and Drug Administration/legislation & jurisprudence

To clarify the approval status of molecular targeted antineoplastic drugs in the United States (U.S.), the European Union (E.U.), and Japan (JP), we checked the status of pediatric indications according to the package insert of each drug. A total of 103 drugs were approved for adult patients in at least one of the three regions whereas only 19 drugs were approved for pediatric patients. Sixty-six of 103 drugs (64.1%) had adult indications in the U.S., the E.U., and JP, whereas only three drugs had pediatric indications in all three regions. Abnormalities in six genes (NRAS, ABL1, JAK2, KIT, ALK and BRAF) were common in childhood cancers as well as adult cancers, for which at least one approved drug could be a potentially actionable drug. Although there were 16 candidate drugs that had adult indications for these abnormalities, only three drugs (18.8%) had pediatric indications. We confirmed that there were few molecular targeted antineoplastic drugs with pediatric indications in the U.S., the E.U., and JP compared with the number of approved drugs for adults. Drugs targeting genomic abnormalities which were common in both adult and pediatric cancers were considered to be good candidates for expansion of their indication for pediatric patients.

Clin Cancer Res. 2013 Mar 15;19(6):1315-25. (PMID: 23329813)
Lancet Oncol. 2018 May;19(5):705-714. (PMID: 29606586)
Int J Cancer. 2015 Mar 1;136(5):E359-86. (PMID: 25220842)
Eur J Pediatr. 2020 May;179(5):839-847. (PMID: 31897842)
Ther Innov Regul Sci. 2016 Sep;50(5):639-647. (PMID: 27274951)
JAMA Intern Med. 2016 Jan;176(1):55-63. (PMID: 26523731)
J Clin Oncol. 2017 Oct 1;35(28):3215-3221. (PMID: 28787259)
J Natl Cancer Inst. 2020 Mar 1;112(3):224-228. (PMID: 31665394)
Nat Rev Drug Discov. 2018 Mar;17(3):183-196. (PMID: 29217837)
Clin Ther. 2014 Feb 1;36(2):163-77. (PMID: 24529288)
Eur J Cancer. 2016 Jul;62:124-31. (PMID: 27258969)
Clin Pharmacol Ther. 2018 Aug;104(2):384-389. (PMID: 29226303)
JCO Precis Oncol. 2017 Jul;2017:. (PMID: 28890946)
Pediatrics. 2014 Mar;133(3):563-7. (PMID: 24567009)
Lancet Oncol. 2020 Apr;21(4):474-476. (PMID: 32192574)
Lancet Oncol. 2020 Feb;21(2):271-282. (PMID: 31838007)
Lancet Oncol. 2017 Jun;18(6):719-731. (PMID: 28410997)
J Mol Diagn. 2015 Sep;17(5):554-9. (PMID: 26320871)
PLoS One. 2018 Jul 27;13(7):e0201425. (PMID: 30052658)
Nature. 2018 Mar 15;555(7696):371-376. (PMID: 29489755)
Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (PMID: 27899662)
Clin Cancer Res. 2019 Dec 15;25(24):7303-7311. (PMID: 31811016)
Cancer Sci. 2018 Sep;109(9):2980-2985. (PMID: 30187675)
Clin Cancer Res. 2019 Jul 1;25(13):3753-3758. (PMID: 30787022)
Nature. 2018 Mar 15;555(7696):321-327. (PMID: 29489754)
Nat Rev Clin Oncol. 2018 Dec;15(12):731-747. (PMID: 30333516)
CA Cancer J Clin. 2018 Nov;68(6):394-424. (PMID: 30207593)
Lancet Oncol. 2017 Jul;18(7):e394-e404. (PMID: 28677575)

0 (Antineoplastic Agents)

Date Created: 20201014 Date Completed: 20210113 Latest Revision: 20210113

20240829

PMC7555892

10.1038/s41598-020-73028-w

33051474