futibatinib (Lytgobi)

Indications

• treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements

Contraindications

• pregnancy

Dosage

• 20 mg PO QD (5 4 mg tablets)
  • swallow whole with or without food

Tabs: 4 mg

Monitor

• ophthalmoscopy including optical coherence tomography (OCT) prior to initiation of therapy, every 2 months for the first 6 months, & every 3 months thereafter

Adverse effects

• common (> 20%)
  • alopecia, dry eye, dry skin, nail toxicity
  • palmar-plantar erythrodysesthesia syndrome
  • musculoskeletal pain, abdominal pain, arthralgia
  • dry mouth, stomatitis dysgeusia, decreased appetite
  • nausea, vomiting, constipation, diarrhea,
  • urinary tract infection
  • fatigue
• laboratory abnormalities (> 20%)
  • increased serum creatinine, serum creatine kinase
  • increased serum ALT, serum AST, serum alkaline phosphatase, serum bilirubin
  • increased activated partial thromboplastin time, international normalized ratio
  • hyperglycemia, hypercalcemia, hyperphosphatemia, hypoalbuminemia
  • anemia, leukopenia, neutropenia, lymphopenia, thrombocytopenia
  • hyponatremnia, hypokalemia, hypoglycemia
• serious
  • retinal pigment epithelium detachment
  • hyperphosphatemia leading to soft tissue calcification
  • embryo-fetal toxicity

Drug interactions

• dual P-glycoprotein & g CYP3A inhibitors
• dual P-glycoprotein & g CYP3A inducers

Mechanism of action

• futibatinib covalently binds to FGFR (FGFR1, FGFR2, FGFR3, FGFR4) & inhibits FGFR phosphorylation & downstream signaling

More general terms

• small inhibitory antineoplastic agent (ib drug)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=71621331
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=134817220