Derazantinib treatment is effective and leads to durable objective responses in patients with inoperable or advanced intrahepatic cholangiocarcinoma with FGFR2 gene fusions or rearrangements, according to primary results from a phase 2 clinical trial called FIDES-01.

These findings were presented on September 16, 2021, by Michele Droz Dit Busset, MD, at the European Society for Medical Oncology (ESMO) Congress 2021. The derazantinib treatment had a manageable safety profile and led to a particularly low incidence of drug-related hand-foot syndrome, stomatitis, and retinal or nail toxicity.

FGFR2 fusions or rearrangements occur in about 15% of intrahepatic cholangiocarcinoma cases, the authors said. Derazantinib is an FGFR1-3 kinase inhibitor and has shown to have broad clinical activity in intrahepatic cholangiocarcinoma patients with FGFR2 fusions, mutations, and amplifications.


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The aim of the FIDES-01 trial was to evaluate the anticancer activity of derazantinib in patients with advanced or inoperable intrahepatic cholangiocarcinoma with tumors that had FGFR2 gene fusions, mutations, or amplifications. These patients were also previously treated with at least one systemic therapy. 

Participants received a 300 mg oral dose of derazantinib once a day. The primary outcome measures were overall response rate and progression-free survival at 3 months. Secondary outcome measures included adverse events, duration of response, progression-free survival, overall survival, health-related quality of life, and objective response.

The trial enrolled 103 patients and primary results showed that it met its primary endpoint with a centrally confirmed overall response rate of 21.4%, which included 22 partial responses. The disease control rate of the treatment was 74.8% and the median duration of response was 6.4 months. The probability of retaining a response for 6 months or more was 68%, median progression-free survival was 7.8 months, and median overall survival was 15.5 months.

The most common adverse reactions associated with the treatment were asthenia or fatigue, elevation in levels of transaminase, nausea, and dry eyes and mouth. The most common grade 3 or less adverse events were transaminase elevations, asthenia or fatigue, hyperphosphatemia, and abdominal pain. Drug-related retinal events, nail toxicities, stomatitis, and hand-foot syndrome were rare.

The study started on November 10, 2017, and is still recruiting participants aged 18 or more years. Participants are in the US, Canada, Belgium, France, Germany, Ireland, Italy, Spain, Switzerland, the UK, and the Republic of Korea. Its estimated date of completion is June 30, 2022.

References

Droz Dit Busset M, Shaib WL, Mody K, et al. Derazantinib for patients with intrahepatic cholangiocarcinoma harboring FGFR2 fusions/rearrangements: Primary results from the phase II study FIDES-01. Poster presented at: ESMO Congress 2021; September 16, 2021; Virtual.

Derazantinib in subjects with FGFR2 gene fusion-, mutation- or amplification- positive inoperable or advanced intrahepatic cholangiocarcinoma (FIDES-01). US National Library of Medicine. Updated August 6, 2021. Accessed September 27, 2021.