Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma
| Autor: | Nevena Damjanov, Sherrie Bhoori, Kyriakos P. Papadopoulos, Terence Hall, Michele Droz dit Busset, Fadi Braiteh, Christian Cotsoglou, Nicola Personeni, William P. Harris, Walid L. Shaib, Yunxia Wang, Brian Schwartz, Vincenzo Mazzaferro, Gianluca Masi, Vittorina Zagonel, Lorenza Rimassa, Julia Kazakin, Bassel F. El-Rayes, Filippo de Braud |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Oncogene Proteins Fusion medicine.medical_treatment Gastroenterology Article Cholangiocarcinoma Fusion gene 03 medical and health sciences Hyperphosphatemia Alkaloids Targeted therapies 0302 clinical medicine Internal medicine medicine Humans In patient Receptor Fibroblast Growth Factor Type 2 Intrahepatic Cholangiocarcinomas Adverse effect Protein Kinase Inhibitors Intrahepatic Cholangiocarcinoma Aged Aged 80 and over Clinical Trials as Topic Chemotherapy Aniline Compounds business.industry Bile duct cancer Middle Aged medicine.disease Bile Ducts Intrahepatic Bile Duct Neoplasms Oncology 030220 oncology & carcinogenesis Mutation Toxicity Quinazolines Female Gene Fusion business |
| Zdroj: | British Journal of Cancer |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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