On September 30, 2022, futibatinib was granted accelerated approval for adults with previously treated, unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements.1
Supporting Efficacy Data
Approval was based on findings in the multicenter TAS-120-101 trial (ClinicalTrials.gov identifier NCT02052778), in which 103 patients received oral futibatinib at 20 mg once daily until disease progression or unacceptable toxicity. The presence of FGFR2 fusions or other rearrangements was determined using next-generation sequencing testing.
OF NOTE
Futibatinib has warnings/precautions for ocular toxicity, hyperphosphatemia and soft-tissue mineralization, and embryofetal toxicity.
On independent review committee assessment, objective responses (all partial) were achieved in 43 patients (42%, 95% confidence interval [CI] = 32%–52%). Median response duration was 9.7 months (95% CI = 7.6–17.1 months); responses persisted for at least 6 months and at least 12 months in 72% and 14% of responders, respectively.
How It Is Used
The presence of an FGFR2 gene fusion or other rearrangement must be confirmed prior to initiation of treatment. The recommended futibatinib dose is 20 mg orally once daily until disease progression or unacceptable toxicity.
Product labeling provides instructions on dosage modification, including dose reduction, for adverse reactions including retinal pigment epithelial detachment, hyperphosphatemia, and other grade 3 or 4 reactions. Coadministration with dual P-glycoprotein and strong CYP3A inhibitors (eg, clarithromycin, erythromycin, diltiazem) and dual P-glycoprotein and strong CYP3A inducers (glucocorticoids, rifampin, carbamazepine) should be avoided.
Safety Profile
Among the 103 patients in TAS-120-101, the most common adverse events of any grade (≥ 20%) were nail toxicity (47%), musculoskeletal pain (43%), constipation (39%), diarrhea (39%), fatigue (37%), dry mouth (35%), alopecia (34%), stomatitis (30%), abdominal pain (30%), dry skin (29%), arthralgia (25%), dysgeusia (25%), dry eye (25%), nausea (24%), decreased appetite (23%), urinary tract infection (23%), palmar-plantar erythrodysesthesia syndrome (21%), and vomiting (20%). The most common grade 3 or 4 adverse events included fatigue (8%), stomatitis (6%), and palmar-plantar erythrodysesthesia syndrome (5%). The most common grade 3 or 4 laboratory abnormalities were increased phosphate (39%), decreased phosphate (20%), decreased sodium (15%), and increased aspartate aminotransferase (13%).
KEY POINTS
- Futibatinib was granted accelerated approval for adults with previously treated, unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene fusions or other rearrangements.
- The recommended futibatinib dose is 20 mg orally once daily until disease progression or unacceptable toxicity.
Serious adverse events occurred in 39% of patients, most commonly pyrexia (3.9%), gastrointestinal hemorrhage (3.9%), ascites (2.9%), musculoskeletal pain (2.9%), and bile duct obstruction (2.9%). Adverse events led to discontinuation of treatment in 4.9% of patients because of esophagitis, oral dysesthesia, bile duct obstruction, dizziness, and anemia.
Futibatinib has warnings/precautions for ocular toxicity, hyperphosphatemia and soft-tissue mineralization, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving futibatinib.
REFERENCE
1. Lytgobi (futibatinib) tablets, prescribing information, Taiho Oncology, Inc, September 2022. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/214801s000lbl.pdf. Accessed on November 16 2022.
