The FDA approved lirafugratinib for adults with previously treated, advanced cholangiocarcinoma harboring an FGFR2 fusion or other rearrangement after the REFOCUS trial showed a 46% ORR.
The FDA approved lirafugratinib (Lyrfigtu; Elevar Therapeutics) for adults with previously treated unresectable, locally advanced or metastatic cholangiocarcinoma harboring a fibroblast growth factor receptor 2 (FGFR2) gene fusion or other rearrangement. The oral kinase inhibitor is given at a recommended dose of 70 mg once daily until disease progression or unacceptable toxicity.1
The approval gives clinicians another targeted treatment option for patients whose disease has progressed after systemic therapy. It also makes the specific FGFR2 alteration central to treatment selection: the indication requires a fusion or other rearrangement, rather than any FGFR2 alteration.1
The FDA based its efficacy assessment on REFOCUS (NCT04526106), a multicenter, open-label, single-arm trial. The analysis included 116 patients with unresectable or metastatic cholangiocarcinoma who had received chemotherapy or chemoimmunotherapy and had not previously received an FGFR inhibitor. Patients took lirafugratinib 70 mg once daily until progression or unacceptable toxicity.1
An independent review committee assessed objective response rate (ORR) and duration of response (DOR) using RECIST version 1.1. The ORR was approximately 46% (95% CI, 36%–55%), and median DOR was 11.8 months (95% CI, 7.5–13.0 months).1 The manufacturer also reported a median progression-free survival of 11.3 months (95% CI, 9.2–14.8 months), although the FDA identified ORR and DOR as the major efficacy outcome measures in its approval notice.2
The single-arm design establishes antitumor activity in the studied population but does not determine whether lirafugratinib improves survival compared with another treatment. Its efficacy results also should not be assumed to apply to patients previously treated with an FGFR inhibitor, who were excluded from the FDA’s efficacy population.1
The FDA highlighted warnings and precautions for ocular toxicity, hyperphosphatemia and soft tissue mineralization, and embryo-fetal toxicity.1 According to safety information released by Elevar, retinal pigment epithelial detachment occurred in 31% of 385 patients who received lirafugratinib, including grade 3 events in 1.8%. The company advises a comprehensive ophthalmologic examination before treatment and regular examinations during therapy, with urgent assessment if visual symptoms develop.2
Hyperphosphatemia was reported in approximately 21% of patients, with a median onset of about 15 days. It is advised that serum phosphate is monitored throughout treatment.2 For oncology pharmacists, counseling should cover prompt reporting of blurred vision or other visual changes, the need for scheduled eye examinations, and adherence to laboratory monitoring. Pharmacists can also help ensure that the documented tumor alteration matches the approved indication and that a patient’s prior FGFR inhibitor exposure is considered when interpreting the trial evidence.
The application received priority review and lirafugratinib received breakthrough therapy and orphan drug designations. The FDA used its Real-Time Oncology Review program and Assessment Aid in evaluating the application.1 The manufacturer is states that the drug is expected to become available in the US by the fourth quarter of 2026.2
