FUTIBATINIB TAB

Clinical Criteria Summary

Unmanageable CYP3A inhibitor/inducer interaction identified
Clinically significant corneal or retinal disorder identified by ophthalmologic examination
Serum phosphate greater than upper limit of normal
Untreated, clinically unstable brain and/or central nervous system metastases
Pregnancy
Breastfeeding

Care provided by a VA or VA Community Care provider of Hematology/Oncology services
Diagnosis of advanced/metastatic or surgically unresectable cholangiocarcinoma
Documented disease progression after at least one platinum-based chemotherapy regimen
Confirmed tumor expression of Fibroblast Growth Factor Receptor 2(FGFR2) fusion or select rearrangement by FDA-approved next generation sequencing
Baseline ophthalmology exam, including optical coherence tomography (OCT) has been performed
Goals of care and role of palliative care consult have been discussed and documented
Eastern Cooperative Oncology Group Performance Status 0 or 1

For women of childbearing potential: Pregnancy should be excluded prior to receiving futibatinib and the patient provided contraceptive counseling on potential risks vs. benefits of taking futibatinib if patient were to become pregnant.
Advise women not to breastfeed during treatment with futibatinib and for 1 week after the last dose.

Adults with previously treated, unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma (iCCA)
Must harbor FGFR2 gene fusions or other rearrangements identified prospectively by DNA testing
Must have disease progression after ≥1 prior regimen including gemcitabine plus platinum-based chemotherapy
Must have radiographically measurable disease per RECIST v 1.1

Starting dose: 20mg/day (5 tablets) once daily until disease progression or unacceptable toxicity occurs
Administered in 21-day cycles with no days off
Treatment interruptions and/or dose reduction indicated for any grade 3 or grade 4 laboratory related events
No dose adjustments recommended for renal or hepatic failure

Monitor serum phosphate and adjust dose based on severity (hyperphosphatemia median onset day 5)
Initiation of phosphate lowering therapy is likely
Perform comprehensive ophthalmologic examination including optical coherence tomography (OCT) prior to initiation, every 2 months for first 6 months, every 3 months thereafter, and urgently at any time for visual symptoms
Advise patients of reproductive potential regarding fetal risk and require use of effective contraception

No boxed warnings or contraindications listed
Hyperphosphatemia occurred in 85% of patients; adverse effects leading to treatment discontinuation were uncommon (2%)
Risk of retinal pigment epithelial detachment (RPED)
Can cause fetal harm

Avoid dual P-gp and strong CYP3A inhibitors (e.g., itraconazole) due to increased futibatinib exposure and adverse effects
Avoid dual P-gp and strong CYP3A inducers (e.g., rifampin) due to decreased futibatinib exposure and reduced efficacy