Derazantinib Shows PFS Efficacy in FGFR2+ Intrahepatic Cholangiocarcinoma


Derazantinib, an FGFR inhibitor, was associated with a median progression-free survival (PFS) of 7.8 months in patients with FGFR2-positive intrahepatic cholangiocarcinoma.

FGFR inhibition with derazantinib (AR 087) led to a survival benefit in patients with locally advanced or metastatic intrahepatic cholangiocarcinoma (iCCA), according to findings from the phase 2 FIDES-01 study (NCT03230318) presented during the 2022 ESMO Congress.

Patients with iCCA harboring FGFR2 fusions (cohort 1; n = 103) the median progression-free survival (PFS) was 7.8 months (95% CI, 5.5-8.3) and the 6-month PFS rate was 53.9% (95% CI, 42.8%-63.7%). Patients with iCAA with FGFR mutations or amplifications (cohort 2; n = 44) experienced a median PFS of 8.3 months (95% CI, 3.5-16.7) and a 6-months PFS rate of 53.9% (95% CI, 42.8%-63.7%). At a follow-up of 12 months, the PFS rate was 18.8% (10.1-29.5) and 44.5% (20.4%-66.1%) in cohort 1 and cohort 2, respectively.

Additionally, patients in cohort 1 achieved an overall response rate (ORR) of 22.3% (95% CI, 14.7%-31.6%) and a disease control rate (DCR) of 75.7% (95% CI, 66.3%-83.6%). Patients in cohort 2 experienced an ORR of 6.8% (95% CI, 1.4%-18.7%) and the DCR was 63.6% (95% CI, 47.8%-77.6%). The median overall survival (OS) was 17.2 months vs 15.9 months, respectively.

Stable disease was reported in 53.4% of patients in cohort 1 and 56.8% in cohort 2. The progressive disease rates were 15.5% and 20.5%, respectively, and the median duration of response was 6.4 months and 5.6 months, respectively.

Only 1 patient in cohort 2 achieved a complete response (CR); this patient had nonmeasurable disease per RECIST 1.1 criteria. No patients experienced a CR in cohort 1. There was no postbaseline assessment for 7.8% of patients with FGFR2 fusions and for 15.9% of patients with FGFR2 mutations or amplifications.

Derazantinib is an investigational oral inhibitor of FGFR1FGFR2, and FGFR3. The agent is being developed under the FIDES program, which also includes patients with urothelial and gastric cancer harboring various FGFR genetic aberrations in addition to patients with iCCA.

Activated FGFRs are a promising potential therapeutic target as deregulation of the FGFR signaling pathway is implicated in iCCA. There are an estimated 10% to 16% of patients with iCCA have FGFR2 fusions with mutations and amplifications in 4% of patients; however smaller series have shown an incidence range of 8% to 13%.

FIDES-01 enrolled patients aged 18 years and older with locally advanced or metastatic iCCA or with combined hepatocellular-cholangiocarcinoma. Eligible patients had an ECOG performance status of 0 or 1 and adequate hematological laboratory values. Patients in both cohorts self-administered derazantinib 300 mg daily until progression, unacceptable toxicity, or withdrawal. Treatment cycles were 28 days with cohort 1 receiving a median of 7 cycles and cohort 2 receiving 5. Tumors were measured by CT or MRI every 8 weeks for the first 6 months of treatments and ever 12 weeks after to determine ORR.

The primary end point of cohort 1 was ORR. In cohort 2 the primary end point was PFS.

The median age was 56 years (range, 28-84) and 63.5 years (range, 28-80) in cohort 1 and cohort 2, respectively. Most patients in both cohorts were women (65% and 57%, respectively).

Regarding safety, at least 1 adverse event (AE) was experienced by 88% of patients overall, and 32% experienced a grade 3 or higher event. The most common AEs of any grade were hyperphosphatemia/blood phosphorus increased (35%), fatigue/asthenia (33%), nausea (32%), dry mouth (27%), and dry eye (24%). Increases in AST and ALT were common grade 3 or higher AEs with 10% of patients experiencing an AST increase and 9% experiencing an ALT increase.

Investigators determined that the drug had a manageable safety profile noting a low amount of the FGFR-inhibitor-class effects including nail toxicities (7.5%), stomatitis (2.0%), retinal events (1.4%), and palmar-plantar erythrodyesthesia (1.4%).


Borad MJ, Javle M, Shaib WL, et al. Efficacy of derazantinib in intrahepatic cholangiocarcinoma (iCCA) patients with FGFR2 fusions, mutations or amplifications. Ann Oncol. 2022;33(suppl 7):S567-S568. doi:10.1016/j.annonc.2022.07.087

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