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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Perspective

Futibatinib: A Potent and Irreversible Inhibitor of Fibroblast Growth Factor Receptors for Treatment of the Bile Duct Cancer

Author(s): Surya K. De*

Volume 31, Issue 6, 2024

Published on: 24 May, 2023

Page: [666 - 670] Pages: 5

DOI: 10.2174/0929867330666230416152913

Abstract

Cholangiocarcinoma is a rare type of cancer. Futibatinib is an irreversible, potent, selective inhibitor of fibroblast growth factor receptors (FGFR 1-4). On September 30, 2022, the US FDA first approved futibatinib to treat adult patients with bile duct cancer whose disease is unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene mutations or other classes of rearrangements. The approval of this medicine was based on phase 3 clinical trial results including an overall response rate (ORR) of 42% and a duration of response (DoR) of 9.7 months. This short perspective summarizes Futibatinib’s synthesis, physicochemical properties, dosage, route of administration, mechanism of action, binding mode, pharmacodynamics, pharmacokinetics, drug interactions, adverse events, and possible mechanism of resistance.

Keywords: Cholangiocarcinoma, futibatinib, fibroblast growth factor receptor, pharmacodynamics, pharmacokinetics, drug interactions.

« Previous Next »
[1]
Bergquist, A.; von Seth, E. Epidemiology of cholangiocarcinoma. Best Pract. Res. Clin. Gastroenterol., 2015, 29(2), 221-232.
[http://dx.doi.org/10.1016/j.bpg.2015.02.003] [PMID: 25966423]
[2]
Razumilava, N.; Gores, G.J. Cholangiocarcinoma. Lancet, 2014, 383(9935), 2168-2179.
[http://dx.doi.org/10.1016/S0140-6736(13)61903-0] [PMID: 24581682]
[3]
Cardinale, V.; Semeraro, R.; Torrice, A.; Gatto, M.; Napoli, C.; Bragazzi, M.C.; Gentile, R.; Alvaro, D. Intra-hepatic and extra-hepatic cholangiocarcinoma: New insight into epidemiology and risk factors. World J. Gastrointest. Oncol., 2010, 2(11), 407-416.
[http://dx.doi.org/10.4251/wjgo.v2.i11.407] [PMID: 21160904]
[4]
Liu, C.; Wang, J.; Ou, Q.J. Possible stem cell origin of human cholangiocarcinoma. World J. Gastroenterol., 2004, 10(22), 3374-3376.
[http://dx.doi.org/10.3748/wjg.v10.i22.3374] [PMID: 15484322]
[5]
Khan, S.A.; Tavolari, S.; Brandi, G. Cholangiocarcinoma: Epidemiology and risk factors. Liver Int., 2019, 39(S1)(Suppl. 1), 19-31.
[http://dx.doi.org/10.1111/liv.14095] [PMID: 30851228]
[6]
Lowery, M.A.; Ptashkin, R.; Jordan, E.; Berger, M.F.; Zehir, A.; Capanu, M.; Kemeny, N.E.; O’Reilly, E.M.; El-Dika, I.; Jarnagin, W.R.; Harding, J.J.; D’Angelica, M.I.; Cercek, A.; Hechtman, J.F.; Solit, D.B.; Schultz, N.; Hyman, D.M.; Klimstra, D.S.; Saltz, L.B.; Abou-Alfa, G.K. Comprehensive molecular profiling of intrahepatic and extrahepatic cholangiocarcinomas: Potential targets for intervention. Clin. Cancer Res., 2018, 24(17), 4154-4161.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-0078] [PMID: 29848569]
[7]
Meric-Bernstam, F.; Bahleda, R.; Hierro, C.; Sanson, M.; Bridgewater, J.; Arkenau, H.T.; Tran, B.; Kelley, R.K.; Park, J.O.; Javle, M.; He, Y.; Benhadji, K.A.; Goyal, L. Futibatinib, an irreversible fgfr1–4 inhibitor, in patients with advanced solid tumors harboring FGF/FGFR aberrations: A phase I dose-expansion study. Cancer Discov., 2022, 12(2), 402-415.
[http://dx.doi.org/10.1158/2159-8290.CD-21-0697] [PMID: 34551969]
[8]
Sootome, H.; Fujita, H.; Ito, K.; Ochiiwa, H.; Fujioka, Y.; Ito, K.; Miura, A.; Sagara, T.; Ito, S.; Ohsawa, H.; Otsuki, S.; Funabashi, K.; Yashiro, M.; Matsuo, K.; Yonekura, K.; Hirai, H. Futibatinib is a novel irreversible FGFR 1–4 inhibitor that shows selective antitumor activity against FGFR-deregulated tumors. Cancer Res., 2020, 80(22), 4986-4997.
[http://dx.doi.org/10.1158/0008-5472.CAN-19-2568] [PMID: 32973082]
[9]
Bahleda, R.; Meric-Bernstam, F.; Goyal, L.; Tran, B.; He, Y.; Yamamiya, I.; Benhadji, K.A.; Matos, I.; Arkenau, H.T. Phase I, first-in-human study of futibatinib, a highly selective, irreversible FGFR1–4 inhibitor in patients with advanced solid tumors. Ann. Oncol., 2020, 31(10), 1405-1412.
[http://dx.doi.org/10.1016/j.annonc.2020.06.018] [PMID: 32622884]
[10]
Rizzo, A.; Ricci, A.D.; Brandi, G. Futibatinib, an investigational agent for the treatment of intrahepatic cholangiocarcinoma: Evidence to date and future perspectives. Expert Opin. Investig. Drugs, 2021, 30(4), 317-324.
[http://dx.doi.org/10.1080/13543784.2021.1837774] [PMID: 33054456]
[11]
Goyal, L.; Chen, C.T.; Pierce, T.T.; Deshpande, V. Case 8-2021: A 34-year-old woman with cholangiocarcinoma. N. Engl. J. Med., 2021, 384(11), 1054-1064.
[http://dx.doi.org/10.1056/NEJMcpc2027092] [PMID: 33730458]
[12]
Lee, P.C.; Hendifar, A.; Osipov, A.; Cho, M.; Li, D.; Gong, J. Targeting the fibroblast growth factor receptor (fgfr) in advanced cholangiocarcinoma: Clinical trial progress and future considerations. Cancers, 2021, 13(7), 1706.
[http://dx.doi.org/10.3390/cancers13071706] [PMID: 33916849]
[13]
Doi, T.; Shitara, K.; Kojima, T.; Kuboki, Y.; Matsubara, N.; Bando, H.; Yoh, K.; Naito, Y.; Hirai, H.; Kurokawa, Y.; Kato, T.; Morizane, C. Phase I study of the irreversible fibroblast growth factor receptor 1-4 inhibitor futibatinib in Japanese patients with advanced solid tumors. Cancer Sci., 2022, 114(2), 574-585.
[http://dx.doi.org/10.1111/cas.15486] [PMID: 35838190]
[14]
Chen, L.; Zhang, Y.; Yin, L.; Cai, B.; Huang, P.; Li, X.; Liang, G. Fibroblast growth factor receptor fusions in cancer: Opportunities and challenges. J. Exp. Clin. Cancer Res., 2021, 40(1), 345.
[http://dx.doi.org/10.1186/s13046-021-02156-6] [PMID: 34732230]
[15]
Duan, W.; Geng, M.; Wang, Y.; Ai, J.; Fan, J.; Dai, Y.; Ding, J. New compound having fgfr inhibitory activity and preparation and application thereof. WO2017215485A1 2017.
[16]
Sootome, H. Therapeutic agent for fgfr inhibitor-resistant cancer WO2015008844A, 2015.
[17]
Sagara, T.; Ito, S.; Otsuki, S.; Sootome, H. 3,5-disubstituted alkynylbenzene compound and salt thereof. US9108973B2 2013.
[18]
Qu, L.; Chen, X.; Wei, H.; Guo, M.; Dai, S.; Jiang, L.; Li, J.; Yue, S.; Chen, Z.; Chen, Y. Structural insights into the potency and selectivity of covalent pan-FGFR inhibitors. Commun. Chem., 2022, 5(1), 5.
[http://dx.doi.org/10.1038/s42004-021-00623-x] [PMID: 36697561]
[19]
Yamamiya, I.; Lester, R.; Sonnichsen, D.; Mina, M.; He, Y.; Benhadji, K.A. Effect of futibatinib on cardiac repolarization: results of a randomized, controlled, double-blind, qt/qtc, phase 1 study in healthy subjects. Clin. Pharmacol. Drug Dev., 2023, 2(3), 304-313.
[http://dx.doi.org/10.1002/cpdd.1195] [PMID: 36404525]
[20]
Goyal, L.; Shi, L.; Liu, L.Y.; Fece de la Cruz, F.; Lennerz, J.K.; Raghavan, S.; Leschiner, I.; Elagina, L.; Siravegna, G.; Ng, R.W.S.; Vu, P.; Patra, K.C.; Saha, S.K.; Uppot, R.N.; Arellano, R.; Reyes, S.; Sagara, T.; Otsuki, S.; Nadres, B.; Shahzade, H.A.; Dey-Guha, I.; Fetter, I.J.; Baiev, I.; Van Seventer, E.E.; Murphy, J.E.; Ferrone, C.R.; Tanabe, K.K.; Deshpande, V.; Harding, J.J.; Yaeger, R.; Kelley, R.K.; Bardelli, A.; Iafrate, A.J.; Hahn, W.C.; Benes, C.H.; Ting, D.T.; Hirai, H.; Getz, G.; Juric, D.; Zhu, A.X.; Corcoran, R.B.; Bardeesy, N. TAS-120 overcomes resistance to atp-competitive fgfr inhibitors in patients with fgfr2 fusion–positive intrahepatic cholangiocarcinoma. Cancer Discov., 2019, 9(8), 1064-1079.
[http://dx.doi.org/10.1158/2159-8290.CD-19-0182] [PMID: 31109923]
[21]
Kalyukina, M.; Yosaatmadja, Y.; Middleditch, M.J.; Patterson, A.V.; Smaill, J.B.; Squire, C.J. TAS-120 cancer target binding: Defining reactivity and revealing the first fibroblast growth factor receptor 1 (FGFR1) irreversible structure. ChemMedChem, 2019, 14(4), 494-500.
[http://dx.doi.org/10.1002/cmdc.201800719] [PMID: 30600916]
[22]
Lamarca, A.; Barriuso, J.; McNamara, M.G.; Valle, J.W. Molecular targeted therapies: Ready for “prime time” in biliary tract cancer. J. Hepatol., 2020, 73(1), 170-185.
[http://dx.doi.org/10.1016/j.jhep.2020.03.007] [PMID: 32171892]
[23]
Roskoski, R. Jr Properties of FDA-approved small molecule protein kinase inhibitors: A 2023 update. Pharmacol. Res., 2023, 187, 106552.
[http://dx.doi.org/10.1016/j.phrs.2022.106552] [PMID: 36403719]
[24]
Vogel, A.; Segatto, O.; Stenzinger, A.; Saborowski, A. FGFR2 inhibition in cholangiocarcinoma. Annu. Rev. Med., 2023, 27(74), 293-306.
[http://dx.doi.org/10.1146/annurev-med-042921-024707] [PMID: 36170665]

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