icotinib

Icotinib was first synthesized in 2002 by the company Betta Pharma.{{cite web|title=About Us|url=http://betapharma.com/about-us/icotinib/|website=Beta Pharma|access-date=31 October 2017}} The US patent application for the preparation of icotinib and icotinib hydrochloride was filed on December 28, 2012, and granted on July 21, 2015.{{cite patent | inventor = Hu S, Long W, Wang F, Li Z | assign1 = Betta Pharmaceuticals Co Ltd |title=Methods of preparing icotinib and icotinib hydrochloride, and intermediates thereof| country = US | number = 9085588 | gdate = 21 July 2015 }}

Icotinib is a quinazoline derivative that competitively inhibits the ATP binding site of the EGFR receptor protein. EGFR drives malignant growth of cells when mutations occur within the tyrosine kinase domain of this protein. Such mutations cause unchecked cell proliferation, which inappropriately activates the anti-apoptotic Ras signaling pathway. By blocking the binding of ATP to EGFR, icotinib prevents activity of the signal transduction cascade that initiates mitosis.{{cite journal | vauthors = Sordella R, Bell DW, Haber DA, Settleman J | title = Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways | journal = Science | volume = 305 | issue = 5687 | pages = 1163–7 | date = August 2004 | pmid = 15284455 | doi = 10.1126/science.1101637 | bibcode = 2004Sci...305.1163S | s2cid = 34389318 }}

Icotinib is approved in China for the treatment of non-small cell lung cancer in patients with an EGFR mutation who have advanced or metastatic disease.{{cite web|title=Product: Icotinib|url=http://en.bettapharma.com/Product.aspx?cId=58|website=Betta Pharma|access-date=1 November 2017}}

The ICOGEN trial was a double-blind, head-to-head phase III study comparing icotinib with gefitinib in 399 patients across 27 centers in China. Results showed icotinib to have a median progression-free survival of 4.6 months (95% CI 3.5 – 6.3) as compared to gefitinib which has a PFS of 3.4 months (95% CI 2.3 – 3.8). Post-hoc analysis found fewer adverse events with icotinib than gefitinib (61% versus 70% respectively, p = 0.046).{{cite journal | vauthors = Shi Y, Zhang L, Liu X, Zhou C, Zhang L, Zhang S, Wang D, Li Q, Qin S, Hu C, Zhang Y, Chen J, Cheng Y, Feng J, Zhang H, Song Y, Wu YL, Xu N, Zhou J, Luo R, Bai C, Jin Y, Liu W, Wei Z, Tan F, Wang Y, Ding L, Dai H, Jiao S, Wang J, Liang L, Zhang W, Sun Y | display-authors = 6 | title = Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial | journal = The Lancet. Oncology | volume = 14 | issue = 10 | pages = 953–61 | date = September 2013 | pmid = 23948351 | doi = 10.1016/S1470-2045(13)70355-3 }}

The ISAFE trial was a phase IV study evaluating the safety and toxicity of icotinib in 5,549 patients. It showed an overall adverse event rate of 31.5% and response rate of 30% to the drug.{{cite journal | vauthors = Tan F, Gu A, Zhang Y, Jiao SC, Wang CL, He J, Jia X, Zhang L, Peng J, Wu M, Ying K, Wang J, Ma K, Zhang S, You C, Ding L, Wang Y, Shen H, Wan J, Sun Y | display-authors = 6 | title=Safety and efficacy results of a phase IV, open-label, multicenter, safety-monitoring study of icotinib in treating advanced non-small cell lung cancer (NSCLC): ISAFE study|journal=ASCO 2013 Meeting|date=2013|pages=e19161}}

After receiving approval from the FDA to study icotinib in NSCLC patients,{{cite web|title=Icotinib & Phase IV ISAFE Trial Poster|url=http://betapharma.com/wp-content/uploads/2016/04/APLCC-Poster-final.pdf|website=Beta Pharma|access-date=1 November 2017}} a phase 1 study was planned to be conducted at Roswell Park Comprehensive Cancer Center in New York State, however the trial was withdrawn prior to enrollment. No further pursuits of US-based studies of icotinib have transpired since.{{ClinicalTrialsGov|NCT02033148|Icotinib Hydrochloride in Treating Patients With Advanced Cancers}}

Icotinib was approved in China by the SFDA in June, 2011.{{cite journal | vauthors = Chen X, Zhu Q, Liu Y, Liu P, Yin Y, Guo R, Lu K, Gu Y, Liu L, Wang J, Wang Z, Røe OD, Shu Y, Zhu L | display-authors = 6 | title = Icotinib is an active treatment of non-small-cell lung cancer: a retrospective study | journal = PLOS ONE | volume = 9 | issue = 5 | pages = e95897 | date = 16 May 2014 | pmid = 24836053 | doi = 10.1371/journal.pone.0095897 | pmc = 4023939 | bibcode = 2014PLoSO...995897C | doi-access = free }} An indication for icotinib was approved in China by the SFDA in November 2014 as first-line treatment for patients with advanced-stage NSCLC with EGFR mutation.{{cite web|title=Betta Pharmaceuticals received marketing approval of Icotinib indicating for first-line treatment of patients with advanced-stage NSCLC with EGFR mutation|url=http://en.bettapharma.com/NewsDetail.aspx?cId=48&id=1499|website=Betta Pharmaceuticals|access-date=1 November 2017}}

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{{Targeted cancer therapeutic agents}}

{{Growth factor receptor modulators}}

Category:Tyrosine kinase inhibitors

Category:Quinazolines