Derazantinib: an investigational drug for the treatment of cholangiocarcinoma

被引：20

作者：

Braun, Stephan ^{[1
]}

McSheehy, Paul ^{[1
]}

Litherland, Karine ^{[1
]}

McKernan, Phil ^{[1
]}

Forster-Gross, Nicole ^{[1
]}

Bachmann, Felix ^{[1
]}

El-Shemerly, Mahmoud ^{[1
]}

Dimova-Dobreva, Miryana ^{[1
]}

Polyakova, Inessa ^{[1
]}

Hackl, Manuel ^{[1
]}

Zhou, Ping ^{[1
]}

Lane, Heidi ^{[1
]}

Kellenberger, Laurenz ^{[1
]}

Engelhardt, Marc ^{[1
]}

机构：

[1] Basilea Pharmaceut Int Ltd, Dev, Grenzacherstr 487, CH-4058 Basel, Switzerland

来源：

EXPERT OPINION ON INVESTIGATIONAL DRUGS | 2021年 / 30卷 / 11期

关键词：

CSF1R kinase inhibition; derazantinib; FGFR1-3 kinase inhibition; FGFR2; amplifications; fusions; mutations; intrahepatic cholangiocarcinoma; VEGFR2 kinase inhibition; TARGETED THERAPIES; OPEN-LABEL; PHASE-II; FREE DNA; FGFR2; FUSIONS; TRANSLOCATIONS; CHEMOTHERAPY; MULTICENTER; MANAGEMENT;

D O I：

10.1080/13543784.2021.1995355

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Introduction This review evaluates the clinical role of fibroblast growth factor receptor 2 (FGFR2) inhibition with derazantinib in patients with intrahepatic cholangiocarcinoma (iCCA) harboring actionable oncogenic FGFR2 fusions/rearrangements, mutations and amplifications. FGFR inhibitors such as derazantinib are currently being evaluated to address the unmet medical need of patients with previously treated, locally advanced or metastatic iCCA harboring such genetic aberrations. Areas covered We summarize the pharmacokinetics, and the emerging safety and efficacy data of the investigational FGFR inhibitor derazantinib. We discuss the future directions of this novel therapeutic agent for iCCA. Expert Opinion Derazantinib is a potent FGFR1-3 kinase inhibitor which also has activity against colony stimulating factor-1-receptor (CSF1R) and vascular endothelial growfth factor receptor-2 (VEGFR2), suggesting a potentially differentiated role in the treatment of patients with iCCA. Derazantinib has shown clinically meaningful efficacy with durable objective responses, supporting the therapeutic potential of derazantinib in previously treated patients with iCCA harboring FGFR2 fusions/rearrangements, mutations and amplifications. The clinical safety profile of derazantinib was well manageable and compared favorably to the FGFR inhibitor class, particularly with a low incidence of drug-related hand-foot syndrome, stomatitis, retinal and nail toxicity. These findings support the need for increased molecular profiling of cholangiocarcinoma patients.

引用

页码：1071 / 1080

页数：10

共 62 条

[11]

Bragazzi MC., 2012, Translational gastrointestinal cancer, V1, P21, DOI DOI 10.3978/J.ISSN.2224-4778.2011.11.04

[12] Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma [J].

Bridgewater, John ;

Galle, Peter R. ;

Khan, Shahid A. ;

Llovet, Josep M. ;

Park, Joong-Won ;

Patel, Tushar ;

Pawlik, Timothy M. ;

Gores, Gregory J. .

JOURNAL OF HEPATOLOGY, 2014, 60 (06) :1268-1289

[13] Derazantinib for patients with intrahepatic cholangiocarcinoma harboring FGFR2 fusions/rearrangements: Primary results from the phase II study FIDES-01 [J].

Busset, M. Droz Dit ;

Shaib, W. L. ;

Mody, K. ;

Personeni, N. ;

Damjanov, N. ;

Harris, W. P. ;

Bergamo, F. ;

Brandi, G. ;

Masi, G. ;

Halfdanarson, T. R. ;

Tam, V. ;

Goff, L. W. ;

Knox, J. ;

Hollebecque, A. ;

Macarulla Mercade, T. ;

Cantero, F. ;

Saulay, M. ;

Braun, S. ;

Javle, M. ;

Borad, M. .

ANNALS OF ONCOLOGY, 2021, 32 :S376-S376

[14] Efficacy of derazantinib in intrahepatic cholangiocarcinoma patients with FGFR2 mutations or amplifications: Pooled analysis of clinical trials and early access programs [J].

Busset, M. Droz Dit ;

Shaib, W. L. ;

Harris, W. P. ;

Damjanov, N. ;

Borad, M. ;

Vogel, A. ;

Bridgewater, J. A. ;

Sellmann, L. ;

Dadduzio, V. ;

Borner, M. ;

Snider, J. ;

Cantero, F. ;

Saulay, M. ;

Braun, S. ;

Mazzaferro, V. ;

Javle, M. .

ANNALS OF ONCOLOGY, 2020, 31 :S1231-S1231

[15] Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients [J].

Chabon, Jacob J. ;

Simmons, Andrew D. ;

Lovejoy, Alexander F. ;

Esfahani, Mohammad S. ;

Newman, Aaron M. ;

Haringsma, Henry J. ;

Kurtz, David M. ;

Stehr, Henning ;

Scherer, Florian ;

Karlovich, Chris A. ;

Harding, Thomas C. ;

Durkin, Kathleen A. ;

Otterson, Gregory A. ;

Purcell, W. Thomas ;

Camidge, D. Ross ;

Goldman, Jonathan W. ;

Sequist, Lecia V. ;

Piotrowska, Zofia ;

Wakelee, Heather A. ;

Neal, Joel W. ;

Alizadeh, Ash A. ;

Diehn, Maximilian .

NATURE COMMUNICATIONS, 2016, 7

[16] FGFR2 Extracellular Domain In-Frame Deletions Are Therapeutically Targetable Genomic Alterations That Function as Oncogenic Drivers in Cholangiocarcinoma [J].

Cleary, James M. ;

Raghavan, Srivatsan ;

Wu, Qibiao ;

Li, Yvonne Y. ;

Spurr, Liam F. ;

Gupta, Hersh, V ;

Rubinson, Douglas A. ;

Fetter, Isobel J. ;

Hornick, Jason L. ;

Nowak, Jonathan A. ;

Siravegna, Giulia ;

Goyal, Lipika ;

Shi, Lei ;

Brais, Lauren K. ;

Loftus, Maureen ;

Shinagare, Atul B. ;

Abrams, Thomas A. ;

Clancy, Thomas E. ;

Wang, Jiping ;

Patel, Anuj K. ;

Brichory, Franck ;

Chessex, Anne Vaslin ;

Sullivan, Ryan J. ;

Keller, Rachel B. ;

Denning, Sarah ;

Hill, Emma R. ;

Shapiro, Geoffrey, I ;

Pokorska-Bocci, Anna ;

Zanna, Claudio ;

Ng, Kimmie ;

Schrag, Deborah ;

Janne, Pasi A. ;

Hahn, William C. ;

Cherniack, Andrew D. ;

Corcoran, Ryan B. ;

Meyerson, Matthew ;

Daina, Antoine ;

Zoete, Vincent ;

Bardeesy, Nabeel ;

Wolpin, Brian M. .

CANCER DISCOVERY, 2021, 11 (10) :2488-2505

[17] Intrahepatic Cholangiocarcinoma: Management Options and Emerging Therapies [J].

Dodson, Rebecca M. ;

Weiss, Matthew J. ;

Cosgrove, David ;

Herman, Joseph M. ;

Kamel, Ihab ;

Anders, Robert ;

Geschwind, Jean-Francois H. ;

Pawlik, Timothy M. .

JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS, 2013, 217 (04) :736-U344

[18] Genotyping of circulating tumor DNA in cholangiocarcinoma reveals diagnostic and prognostic information [J].

Ettrich, T. J. ;

Schwerdel, D. ;

Dolnik, A. ;

Beuter, F. ;

Blaette, T. J. ;

Schmidt, S. A. ;

Stanescu-Siegmund, N. ;

Steinacker, J. ;

Marienfeld, R. ;

Kleger, A. ;

Bollinger, L. ;

Seufferlein, T. ;

Berger, A. W. .

SCIENTIFIC REPORTS, 2019, 9 (1)

[19]

Farshidfar F, 2017, CELL REP, V18, P2780, DOI [10.1016/j.celrep.2017.02.033, 10.1016/j.celrep.2017.06.008]

[20] Functions of Fibroblast Growth Factor Receptors in cancer defined by novel translocations and mutations [J].

Gallo, Leandro H. ;

Nelson, Katelyn N. ;

Meyer, April N. ;

Donoghue, Daniel J. .

CYTOKINE & GROWTH FACTOR REVIEWS, 2015, 26 (04) :425-449

← 1 2 3 4 5 6 7 →