FDA Approves Futibatinib for Pretreated, Advanced or Metastatic Intrahepatic Cholangiocarcinoma with FGFR2 Rearrangements


Futibatinib is now approved to treat patients with previously treated unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma. The agent comes with warnings for ocular toxicities, and hyperphosphatemia and soft tissue mineralization.

Following frontline treatment, patients with unresectable, locally advanced or metastatic intrahepatic FGFR2-positive cholangiocarcinoma may now undergo treatment with futibatinib (Lytgobi), an oral agent which binds to FGFR2 and inhibits the signaling pathway.1

The FDA approved the agent based on findings from the phase 2 FOENIX*-CCA2 trial (NCT02052778), an open-label trial which evaluated the efficacy and tolerability of futibatinib in 103 patients with unresectable or metastatic disease. According to an independent central review, the objective response rate with futibatinib was 42%. In addition, the median duration of response was 9.7 months, and 72% of responses lasted for 6 months or longer.

The most frequently reported toxicities (≥ 20%) included nail toxicity, musculoskeletal pain, constipation, diarrhea, fatigue, dry mouth, alopecia, stomatitis, dry skin, arthralgia, dysgeusia, abdominal pain, dry eye, nausea, decreased appetite, urinary tract infection, palmar-plantar erythrodysesthesia syndrome, and vomiting.

"[Futibatinib] is a key example of the potential of precision medicine in [intrahepatic cholangiocarcinoma] and represents another advance in the treatment of this rare and challenging disease," said principal investigator, Lipika Goyal, MD, the Massachusetts General Hospital Cancer Center, in a press release. "I am encouraged that treatment options continue to expand and evolve for this disease through the dedicated efforts of many over several years."

Cholangiocarcinoma is an aggressive cancer originating in the bile ducts. Each year, it affects approximately 8,000 individuals in the US—about 20% of whom will have the intrahepatic form of this disease.Among these, around 10-16% are expected to have a FGFR2 gene rearrangement, and thus be eligible for this treatment approach.

Futibatinib is an oral tablet which should be swallowed whole, with or without food.2 The recommended dose is 20 mg (five 4-mg tablets) daily. The first recommended dose reduction is 16 mg daily (four 4-mg tablets) and the second recommended dose reduction is 12 mg (three 4-mg tablets) daily. If a patient cannot tolerate 12 mg, the agent should be discontinued.

Patients should be taught not to crush, chew, or dissolve tablets. If they miss a dose by 12 hours or more, or if they vomit following their dose, they should resume dosing in accordance with the schedule. Extra tablets should not be used to make up for the missed dose. They should also be taught to avoid grapefruit products during treatment; along with dual P-gp and strong CYP31 inhibitors or inducers.

The prescribing label warns against ocular toxicity; retinal pigmen epithelial detachment (RPED) may be a consequence of treatment. Therefore, patients should receive a comprehensive ophthalmological examination including optical coherence tomography (OCT) prior to their treatment initiation, every 2 months for the first 6 months, and every 3 months thereafter to monitor their visual function. Patients should be taught to report any blurred vision, flashes of light, or black spots right away. In addition, 15% of patients (318) experienced dry eye while on the trials. If this occurs, ocular demulcents are recommended.

Patients may also be at risk of hyperphosphatemia and soft tissue mineralization because of increase in phosphate levels. During the trial, 88% of patients were reported to have hyperphosphatemia and the median onset time was 5 days. Patients should be monitored for hyperphosphatemia, and taught to report any new muscle cramps, numbness, or tingling in the mouth. If detected, patient should be started on a low phosphate diet and phosphate lowering therapy. If the serum phosphate levels surpass 7 mg/dL or greater, the dose should be withheld, reduced, or permanently discontinued.

Patients should also be educated on the risk of embryo-fetal toxicity associated with futibatinib.


  1. FDA approves Taiho's Lytgobi (futibatinib) tables for previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma. News release. Taiho Oncology, Inc. September 30, 2022. Accessed September 30, 2022. https://prn.to/3y2s7W8
  2. Lytgobi. Prescribing information. Taiho Oncology, Inc; 2022. Accessed September 30, 2022. https://bit.ly/3BXxase
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