Icotinib (trade name Conmana) is a highly selective, first generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Icotinib is approved for use in China as first-line monotherapy in patients with non-small-cell lung cancer with somatic EGFR mutations.
Development
Icotinib was first synthesized in 2002 by the company
Betta Pharma.[1] The US patent application for the preparation of icotinib and icotinib hydrochloride was filed on December 28, 2012, and granted on July 21, 2015.[2]
Mechanism of action
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 kinasedomain of this protein. Such mutations cause unchecked cell proliferation, which inappropriately activates the
anti-apoptoticRas signaling pathway. By blocking the binding of ATP to EGFR, icotinib prevents activity of the signal transduction cascade that initiates
mitosis.[3]
Indications
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.[4]
Clinical research
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).[5]
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.[6]
After receiving approval from the
FDA to study icotinib in NSCLC patients,[7] 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New York State, however the trial was withdrawn prior to enrollment.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.[8]
Regulatory approvals
Icotinib was approved in China by the
SFDA in June, 2011.[9] 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.[10]
References
^"About Us". Beta Pharma. Retrieved 31 October 2017.
^US 9085588, Hu S, Long W, Wang F, Li Z, "Methods of preparing icotinib and icotinib hydrochloride, and intermediates thereof", issued 21 July 2015, assigned to Betta Pharmaceuticals Co Ltd
^Shi Y, Zhang L, Liu X, Zhou C, Zhang L, Zhang S, et al. (September 2013). "Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial". The Lancet. Oncology. 14 (10): 953–61.
doi:
10.1016/S1470-2045(13)70355-3.
PMID23948351.
^Tan F, Gu A, Zhang Y, Jiao SC, Wang CL, He J, et al. (2013). "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". ASCO 2013 Meeting: e19161.