Patients with rare cancers like intrahepatic cholangiocarcinoma seldom have many additional treatment options if their tumors become resistant to first-line therapy: From August 1, 2021–July 31, 2022, the U.S. Food and Drug Administration (FDA) approved only five new agents or indications for rare tumors. On September 30, 2022, FDA added one more, giving futibatinib (Lytgobi™) accelerated approval for adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements. The approval was based on the drug’s 42% overall response rate and median duration of response of 9.7 months.
Tyrosine kinase inhibitor
Mechanism of Action
Futibatinib is a small molecule kinase inhibitor that binds to and inhibits fibroblast growth factor receptor (FGFR) proteins, which subsequently inhibits phosphorylation, downstream signaling, and viability in cancer cell lines with FGFR gene alterations, including fusions or rearrangements, amplifications, and variants.
Treatment of adult patients with previously treated, unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma with FGFR2 gene fusions or other rearrangements
20 mg (five 4 mg tablets) taken orally once daily until patients experience disease progression or unacceptable toxicity. See the package insert for dose reduction recommendations for adverse events.
Swallow the tablets whole; do not crush, chew, split, or dissolve. Take the tablets with or without food at approximately the same time daily. If you miss a dose by more than 12 hours or if vomit a dose, do not take another dose until your next scheduled time.
More than 20% of the 103 patients in study TAS-120-101 reported nail toxicity, musculoskeletal pain, constipation, diarrhea, fatigue, dry mouth, alopecia, stomatitis, abdominal pain, dry skin, arthralgia, dysgeusia, dry eye, nausea, decreased appetite, urinary tract infection, palmar-plantar erythrodysesthesia syndrome, and vomiting. A clinically relevant adverse reaction of retinal pigment epithelial detachment, which causes blurred vision, occurred in 7.8% of patients.
More than 50% of patients experienced increased phosphate, creatinine, glucose, or calcium and decreased hemoglobin or sodium. See the package insert for additional information. Hyperphosphatemia was reported in 88% of patients with a five-day median time to onset.
Prior to administration, verify the presence of an FGFR2 gene fusion or other rearrangements, typically identified through next-generation sequencing, and pregnancy screening results for patients of reproductive potential. Review the baseline laboratory values and medical history for the presence of moderate or severe renal or hepatic impairment.
Patients must receive a comprehensive ophthalmologic examination with optical coherence tomography (OCT) of the macula at baseline prior to treatment initiation, every two months for the first six months, and every three months thereafter. Immediately refer patients for ophthalmologic evaluation for any new or worsening visual symptoms, such as blurred vision, with close continued follow-up every three weeks or until symptoms resolve or futibatinib is discontinued.
Monitor phosphate levels throughout treatment at intervals determined by prescriber discretion. Initiate a low-phosphate diet and phosphate-lowering therapy for serum phosphate levels of 5.5 mg/dl or greater. Intensify phosphate-lowering therapy and reduce, withhold, or permanently discontinue futibatinib for serum phosphate levels of 7 mg/dl or greater, based on severity and duration of hyperphosphatemia.
Futibatinib is a CYP3A and P-gp substrate; review patients’ medication lists and consult with a pharmacist to ensure that they are not taking any dual P-gp and strong CYP3A inhibitors or inducers. Avoid grapefruit or grapefruit juice.
- If you are of reproductive potential, you must use effective contraception during sexual activity with opposite-sex partners during treatment and for one week following the last dose to prevent pregnancy. If you are lactating, do not breastfeed during treatment and for one week after your last dose.
- Your treatment requires baseline and ongoing ophthalmology evaluations. You must immediately report any new or worsening vision changes, including blurry vision or dry eye.
- You will need to adhere to laboratory surveillance and a low-phosphate diet and you may require phosphate-binding agents if your phosphate levels increase. Notify your care team of new or worsening symptoms of increased phosphate levels, including muscle cramps, numbness, or tingling around the mouth.
- You may develop nail disorders, including dystrophy, hypertrophy, infection, pain, breakage, detachment from the nail bed, or changes in pigmentation.
- Avoid grapefruit products and notify your care team of all prescription medications, over-the-counter drugs, herbal products, or vitamin supplements.
In the drug’s clinical trials, no overall differences in safety or effectiveness were observed in patients aged 65 or older (22%) and younger adult patients. Futibatinib has not been studied for use in pediatric patients.
Formal carcinogenicity and fertility studies have not been conducted with futibatinib. Nurses should use their institution’s safe handling and disposal precautions.
Visit Taiho Oncology Patient Support or call 844-TAIHO-4U (844-824-4648).