Lirafugratinib was added as a category 2A subsequent-line option for cholangiocarcinoma with an FGFR2 fusion or rearrangement and disease progression.
Lirafugratinib has been added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Biliary Tract Cancers as a category 2A preferred subsequent-line therapy for patients with cholangiocarcinoma (CCA) who have an FGFR2 fusion or other rearrangement and disease progression.1,2
The recommendation follows the September 23, 2026,
“We are pleased that lirafugratinib was promptly added to the guidelines upon FDA approval,” Rose Lai, MD, senior vice president of clinical development at Elevar Therapeutics, stated in a news release.1
Lirafugratinib is an oral, irreversible, selective FGFR2 inhibitor.⁴ The indication is for adult patients with CCA that is unresectable, locally advanced or metastatic, previously treated, and harbors an FGFR2 gene fusion or other rearrangement.³ The recommended dose is 70 mg orally once daily until disease progression or unacceptable adverse effects.
ReFocus was an open-label trial that included dose-escalation, dose-expansion (in CCA), and extension portions.⁴ Patients were 18 years or older, had unresectable or metastatic CCA or another solid tumor, had an ECOG performance status of 0 or 1, and had an FGFR2 alteration documented by local assessment. The pivotal cohort (n = 116) comprised patients with FGFR2 fusion or rearrangement CCA who had received prior chemotherapy and were naive to FGFR inhibitors, drawn from dose-escalation cohort 2 (n = 4), dose-expansion group 2A (n = 26), and extension group 2A (n = 86).
Lirafugratinib in CCA: Highlights
The primary end point was confirmed ORR per RECIST 1.1 criteria by independent review committee (IRC), and key secondary end points were DOR, disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and quality of life. The primary efficacy analysis included 114 patients. In that set, the median age was 57 years (range, 29-81), 61.4% of patients were female, and 50.0% of patients had an ECOG performance status of 0. Patients had received a median of 1 prior line of systemic therapy (range, 1-5), and 33.3% had previously received gemcitabine plus platinum chemotherapy with an immune checkpoint inhibitor.
The DCR was 96.5% (95% CI, 91.3%-99.0%). The median PFS was 11.3 months (95% CI, 9.2-14.8), and the 12-month PFS rate was 49.2%.1,4 The median OS was 22.8 months (95% CI, 18.1-27.2).⁴
In a supportive analysis group of patients with prior FGFR inhibitor exposure (n = 53), the ORR was 22.6% (95% CI, 12.3%-36.2%), the median DOR was 5.6 months (95% CI, 3.8-not evaluable), and the median PFS was 5.6 months (95% CI, 3.7-7.4).
In the pivotal safety population (n = 116), any-grade treatment-related adverse effects (TRAEs) occurred in 100% of patients, and grade 3 or higher TRAEs were reported in 57.8% of patients. TRAEs led to dose reductions in 75.9%, dose interruptions in 82.8%, and discontinuation in 4.3% of patients, and no TRAE led to death.
The most common on-target AEs were nail toxicities (any-grade, 87.9%; grade ≥ 3, 12.1%), palmar-plantar erythrodysesthesia syndrome (PPES; 81.9%; 32.8%), stomatitis (78.4%; 12.1%), and retinal pigment epithelial detachment (37.1%; 1.7%). Hyperphosphatemia occurred in 20.7% of patients, with no grade 3 or higher events. PPES and stomatitis were the most common TRAEs leading to dose interruption, in 54.3% and 21.6% of patients, respectively.
The prescribing warnings include ocular toxicity, hyperphosphatemia and soft tissue mineralization, and embryo-fetal toxicity.³ Macular optical coherence tomography is recommended before treatment, every 2 months for the first 13 months, and every 4 months thereafter.¹
