Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma

Background Next-generation sequencing has identified actionable genetic aberrations in intrahepatic cholangiocarcinomas (iCCA), including the fibroblast growth factor receptor 2 (FGFR2) fusions. Derazantinib (ARQ 087), an orally bioavailable, multi-kinase inhibitor with potent pan-FGFR activity, has...

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Vydáno v:British journal of cancer Ročník 120; číslo 2; s. 165 - 171
Hlavní autoři: Mazzaferro, Vincenzo, El-Rayes, Bassel F., Droz dit Busset, Michele, Cotsoglou, Christian, Harris, William P., Damjanov, Nevena, Masi, Gianluca, Rimassa, Lorenza, Personeni, Nicola, Braiteh, Fadi, Zagonel, Vittorina, Papadopoulos, Kyriakos P., Hall, Terence, Wang, Yunxia, Schwartz, Brian, Kazakin, Julia, Bhoori, Sherrie, de Braud, Filippo, Shaib, Walid L.
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 22.01.2019
Nature Publishing Group
Témata:
631/67/1059/602
692/4028/67/1504/1329/1326
Adult
Aged
Aged, 80 and over
Alkaloids - administration & dosage
Alkaloids - adverse effects
Asthenia
Biomedical and Life Sciences
Biomedicine
Cancer Research
Chemotherapy
Cholangiocarcinoma
Cholangiocarcinoma - drug therapy
Cholangiocarcinoma - genetics
Cholangiocarcinoma - pathology
Clinical Trials as Topic
Disease control
Drug Resistance
Enzyme inhibitors
Epidemiology
Fatigue
Female
Fibroblast growth factor receptor 2
Fibroblast growth factor receptors
Gene fusion
Humans
Hyperphosphatemia
Kinases
Male
Middle Aged
Molecular Medicine
Mutation
Next-generation sequencing
Oncogene Proteins, Fusion - drug effects
Oncogene Proteins, Fusion - genetics
Oncology
Patients
Protein Kinase Inhibitors - administration & dosage
Protein Kinase Inhibitors - adverse effects
Receptor, Fibroblast Growth Factor, Type 2 - genetics
Toxicity
Tumors
ISSN:0007-0920, 1532-1827, 1532-1827
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Shrnutí:Background Next-generation sequencing has identified actionable genetic aberrations in intrahepatic cholangiocarcinomas (iCCA), including the fibroblast growth factor receptor 2 (FGFR2) fusions. Derazantinib (ARQ 087), an orally bioavailable, multi-kinase inhibitor with potent pan-FGFR activity, has shown preliminary therapeutic activity against FGFR2 fusion-positive iCCA. Methods This multicentre, phase 1/2, open-label study enrolled adult patients with unresectable iCCA with FGFR2 fusion, who progressed, were intolerant or not eligible to first-line chemotherapy (NCT01752920). Subjects received derazantinib in continuous daily doses. Tumour response was assessed according to RECIST 1.1 every 8 weeks. Results Twenty-nine patients (18 women/11 men; median age, 58.7 years), 2 treatment-naive and 27 who progressed after at least one prior systemic therapy, were enrolled. Overall response rate was 20.7%, disease control rate was 82.8%. Estimated median progression-free survival was 5.7 months (95% CI: 4.04–9.2 months). Treatment-related adverse events (AE) were observed in 27 patients (93.1%, all grades), including asthenia/fatigue (69.0%), eye toxicity (41.4%), and hyperphosphatemia (75.9%). Grade ≥ 3 AEs occurred in 8 patients (27.6%). Conclusion Derazantinib demonstrated encouraging anti-tumour activity and a manageable safety profile in patients with advanced, unresectable iCCA with FGFR2 fusion who progressed after chemotherapy. A pivotal trial of derazantinib in iCCA is ongoing (NCT03230318).
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0007-0920
1532-1827
1532-1827
DOI:10.1038/s41416-018-0334-0