FDA Approves Lirafugratinib for Previously Treated FGFR2-Rearranged Cholangiocarcinoma. The Evidence Is a Single-Arm Trial.
The FDA approved lirafugratinib (Lyrfigtu) on Sept. 23 for previously treated cholangiocarcinoma with an FGFR2 fusion or rearrangement, based on a 116-patient single-arm trial with a 46 percent response rate. No FDA-authorized test exists, so testing is the first step.
On Sept. 23, the Food and Drug Administration approved lirafugratinib (Lyrfigtu, Elevar Therapeutics) for adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma that harbors an FGFR2 gene fusion or other rearrangement. The dose is 70 mg once daily until progression or unacceptable toxicity.
The approval rests on one single-arm, open-label trial. The FDA granted priority review under its Real-Time Oncology Review program, and the drug holds breakthrough therapy and orphan designations. Medscape reported that lirafugratinib joins two FGFR2-directed inhibitors already on the market: pemigatinib, with the same previously treated indication, and futibatinib, limited to intrahepatic disease. The manufacturer expects the drug to be available in the United States by the fourth quarter of 2026, Pharmacy Times reported.
What the trial showed
REFOCUS (NCT04526106) enrolled 116 patients with unresectable or metastatic cholangiocarcinoma who had received prior chemotherapy or chemoimmunotherapy and had not been treated with an FGFR inhibitor. All had received at least one prior platinum-based regimen, per the prescribing information.
The major efficacy measures were objective response rate and duration of response, assessed by independent review under RECIST v1.1. The response rate was 46 percent (95% CI 36 to 55), and median duration of response was 11.8 months (95% CI 7.5 to 13.0). Median time to response was 1.9 months.
The manufacturer also reports a median progression-free survival of 11.3 months (95% CI 9.2 to 14.8), according to Pharmacy Times. OncLive reported a median overall survival of 22.8 months among 114 evaluable patients, from data presented at the 2026 ASCO Gastrointestinal Cancers Symposium. With no control arm, neither figure can be credited to the drug.
REFOCUS shows that tumors shrink and that responses can last. With no comparator arm, it cannot show how lirafugratinib compares with pemigatinib or futibatinib.
Safety and the label
The label carries warnings for ocular toxicity, hyperphosphatemia with soft tissue mineralization, and embryo-fetal toxicity. Among 385 patients across solid tumors, retinal pigment epithelial detachment occurred in 31 percent, with a median onset of 57 days. The label calls for a comprehensive eye examination including macular optical coherence tomography before treatment, every two months for the first 13 months and every four months after that. Hyperphosphatemia occurred in 21 percent, with a median onset of 15 days.
In the 116 cholangiocarcinoma patients, 32 percent had serious adverse reactions, and one had a fatal hemorrhage. Five percent permanently discontinued, and 88 percent needed a dose interruption. Nail toxicity (89 percent), palmar-plantar erythrodysesthesia (82 percent, grade 3 or 4 in 33 percent) and stomatitis (80 percent) led the list. Strong or moderate CYP3A inhibitors and inducers should be avoided, with a lower dose if an inhibitor cannot be.
When to order FGFR2 testing
The label says to confirm an FGFR2 fusion or rearrangement before starting treatment and notes that an FDA-authorized test for this purpose is not available. In REFOCUS, 112 of 116 patients were identified by next-generation sequencing, and qualifying rearrangements had a breakpoint that left the FGFR2 kinase domain intact.
Because the drug is a second-line option, a result ordered at diagnosis of advanced disease is in hand before first-line therapy fails. Ordered at progression, it can delay the next decision.
What it means in clinic
Check whether your laboratory's panel detects FGFR2 rearrangements and how, and ask for the test at diagnosis of advanced disease rather than at progression. Confirm that ophthalmology with optical coherence tomography is available before a first prescription is written. Review the medication list for CYP3A interactions.
The trial enrolled only patients who had not received an FGFR inhibitor, so it does not speak to use after pemigatinib or futibatinib. Practices should confirm coverage and specialty pharmacy access ahead of the launch. For another recent oncology approval built on a defined molecular subgroup, see our report on adjuvant atezolizumab in dMMR colon cancer.
Reported, fact-checked and edited by The Script Pad's editorial staff.
This article is for professional education and does not replace clinical judgment. Treatment decisions should be based on the individual patient and current guidelines.
