Futibatinib, Pemigatinib, Lirafugratinib Yield Similar PFS in FGFR-Altered Biliary Tract Cancers

Futibatinib (Lytgobi), pemigatinib (Pemazyre), and lirafugratinib (Lyrfigtu) showed similar objective response rates (ORRs) and progression-free survival (PFS) at first exposure in patients with biliary tract cancers and FGFR alterations, according to a retrospective analysis from a single academic center.¹ No significant differences were observed in PFS or overall survival (OS) across the 3 agents.

Faustine Nouvel, of the Department of Medical Oncology at Gustave Roussy, presented the findings in a poster at the 2026 European Society for Medical Oncology (ESMO) Congress.

How did the FGFR inhibitors compare?

At first exposure, the ORR was 56.2% (95% CI, 29.9%-80.2%) with pemigatinib, 38.9% (95% CI, 17.3%-64.3%) with futibatinib, and 58.3% (95% CI, 27.7%-84.8%) with lirafugratinib. Median PFS was 8.5 months (95% CI, 6.4-17.5) with pemigatinib, 8.3 months (95% CI, 5.8-16.7) with futibatinib, and 9.1 months (95% CI, 5.6-not reached [NR]) with lirafugratinib; no significant difference was observed across the 3 agents (P = .70).

Overall, the median OS from diagnosis in the FGFR-altered population was 38.4 months (95% CI, 32.4-55.3). From first exposure, median OS was 32.7 months (95% CI, 19.2-NR) in the pemigatinib cohort; it was 18.9 months (95% CI, 10.3-NR) with futibatinib and 25.4 months (95% CI, 19.3-NR) with lirafugratinib (P = .13).

What were the characteristics of the FGFR-altered cohort?

Among 754 patients with biliary tract cancer, 100 (13%) had FGFR alterations. In the FGFR-altered cohort, 61% were female, median age at diagnosis was 58 years (IQR, 50-67), 79% had intrahepatic disease, and 66% had synchronous metastases.

Across the entire cohort, FGFR alterations were fusions only in 47%, mutations only in 38%, and fusion plus mutation in 15%. FGFR2 alterations predominated, with fusions in 55% of patients and mutations in 36%. FGFR3 fusions and mutations occurred in 6% and 10%, respectively, followed by FGFR1 (fusions, 1%; mutations, 6%) and FGFR4 (fusions, 3%; mutations, 2%).

A total of 61 patients (61%) received at least 1 FGFR inhibitor; among them, 19 (31%) received sequential FGFR inhibition. Futibatinib was used at later treatment lines than pemigatinib, with median lines of 4 and 2, respectively; the median line for lirafugratinib was 3. Most patients who received an FGFR inhibitor had FGFR2 fusions, including all of those treated with pemigatinib and 84.4% of those treated with futibatinib.

How was the retrospective analysis conducted?

The investigators retrospectively analyzed patients with FGFR1 to 4 alterations treated at an academic center. ORR was assessed per RECIST criteria, and PFS and OS were estimated using Kaplan-Meier analysis with a log-rank test. Efficacy analyses were restricted to the first FGFR inhibitor exposure to limit treatment-line bias.

What did the investigators conclude?

In the abstract, the investigators wrote that FGFR2 fusions predominated in the cohort and that “the 3 main FGFR inhibitors showed similar ORR and PFS at first exposure.”¹ They attributed the numerically longer OS with pemigatinib to “treatment-line differences and limited sample size.”¹ They added that prospective or pooled analyses are needed to compare FGFR inhibitors and assess sequential inhibition strategies.

What is the regulatory landscape for FGFR2 inhibitors in cholangiocarcinoma?

Most recently, in September 2026, the FDA approved lirafugratinib in previously treated unresectable, locally advanced or metastatic cholangiocarcinoma harboring an FGFR2 gene fusion or other rearrangement.² This approval joined the September 2022 accelerated approval of futibatinib and the April 2020 approval of pemigatinib.^3,4

References

1. Nouvel F, Hollebecque A, Smolenschi C, et al. Futibatinib, pemigatinib, or lirafugratinib for patients with biliary tract cancers and FGFR alterations. Presented at: 2026 European Society for Medical Oncology Congress; October 23-27, 2026; Madrid, Spain. Abstract 479P.
2. FDA approves lirafugratinib for previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma. News release. FDA. September 23, 2026. Accessed October 27, 2026. https://tinyurl.com/mst6kcav
3. FDA approves Taiho's LYTGOBI® (futibatinib) tablets for previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma. News release. Taiho Oncology, Inc. September 30, 2022. Accessed October 27, 2026. https://tinyurl.com/ks9sz6a5
4. FDA approves Incyte’s Pemazyre™ (pemigatinib) as first targeted treatment for adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma. News release. Incyte. April 17, 2020. Accessed October 27, 2026. https://tinyurl.com/54repke5