Lirafugratinib Receives NCCN Category 2A Recommendation Following FDA Approval in FGFR2-Altered Cholangiocarcinoma
Clinical Summary:
- Guideline Update: The National Comprehensive Cancer Network (NCCN) added lirafugratinib as a Category 2a preferred subsequent-line treatment option, useful in certain circumstances, for patients with cholangiocarcinoma harboring FGFR2 fusions or other rearrangements following disease progression.
- Key Outcomes: The update follows FDA approval supported by results from the phase 1/2 ReFocus trial, in which lirafugratinib demonstrated a confirmed objective response rate of 46%, median duration of response of 11.8 months, and median progression-free survival of 11.3 months.
- Clinical Relevance: This guideline update reinforces the role of FGF2-targeted therapy in previously treated cholangiocarcinoma and supports molecular testing to identify patients who may benefit from lirafugratinib.
The National Comprehensive Cancer Network (NCCN) has updated its Clinical Practice Guidelines in Oncology to include lirafugratinib (Lyrfigtu; Elevar Therapeutics) as a Category 2A preferred subsequent-line treatment option, useful in certain circumstances, for patients with cholangiocarcinoma harboring FGFR2 fusions or other rearrangements following disease progression.
The November 3, 2026, announcement follows the recent Food and Drug Administration (FDA) approval of lirafugratinib on September 23, 2026, supported by findings from the phase 1/2 ReFocus trial.
In the population supporting the FDA-approved indication (n = 385), lirafugratinib demonstrated a confirmed objective response rate (ORR) of 46%. Median duration of response was 11.8 months, demonstrating sustained antitumor activity among patients who achieved a response. Median progression-free survival (PFS) was 11.3 months, and the 12-month PFS rate was 49.2%.
The safety profile of lirafugratinib was reported to be manageable through dose adjustments. The biggest safety consideration was ocular toxicities including retinal pigment epithelial detachment (31%; 1.8% grade 3), dry eye (38%), blurred vision (18%), and corneal toxicity or keratitis (11%).
The median time to first onset of retinal pigment epithelial detachment was 57 days. Retinal pigment epithelial detachment led to dose interruption in 15% of patients and dose reductions in 10% of patients.
The prescribing information recommends comprehensive ophthalmologic examinations, including optical coherence tomography of the macula, before treatment initiation, every 2 months during the first 13 months, and every 4 months thereafter.
Hyperphosphatemia occurred in 21% of patients, with a median time to onset of 15 days. The prescribing information recommends monitoring serum phosphate throughout treatment and managing elevated levels as clinically appropriate.
Serious adverse reactions occurred in 32% of patients. The most frequently reported serious adverse reactions included infection (6%), pneumonia (3.4%), fatigue (2.6%), and hemorrhage (2.6%). One fatal adverse reaction involving hemorrhage was reported.
The prescribing information also includes warnings and precautions for soft tissue mineralization and embryo-fetal toxicity.
Lirafugratinib is an oral, selective FGFR2 inhibitor developed for patients with FGFR2-altered malignancies. The NCCN inclusion of lirafugratinib reinforces its role as a biomarker-directed treatment option for patients with cholangiocarcinoma harboring FGFR2 fusions or other rearrangements following disease progression.
Source:
Elevar Therapeutics. Elevar Therapeutics announces Lirafugratinib (Lyrfigtu) added to NCCN clinical practice guidelines in oncology (NCCN Guidelines) as second-line therapy for cholangiocarcinoma with FGFR2 fusion or other rearrangement. Accessed on: November 4, 2026. https://elevartx.com/2026/11/03/elevar-lyrfigtu-nccn-guidelines/
