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- Title
Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma.
- Authors
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.
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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%).<bold>Conclusion: </bold>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).
- Publication
British Journal of Cancer, 2019, Vol 120, Issue 2, p165
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/s41416-018-0334-0