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Observational Study
. 2025 Sep;45(9):e70295.
doi: 10.1111/liv.70295.

Ivosidenib for IDH1-Mutant Intrahepatic Cholangiocarcinoma: Insights From a Multicenter Real-World Study

Monica Niger  1 , Margherita Rimini  2 , Florian Castet  3 , Anna Melzer  4   5 , Mario Domenico Rizzato  6 , Tiziana Pressiani  7 , Daniele Lavacchi  8 , Giuseppe Aprile  9 , Torsello Angela  10 , Tiziana Saladino  11 , Noventa Silvia  12 , Pasqua Cito  13 , Alessandro Pastorino  14 , Eduardo Terán-Brage  3 , Carolina Sciortino  1 , Silvia Camera  2 , Chiara Pircher  1 , Mara Persano  2 , Vincenzo Mazzaferro  15   16 , Silvia Foti  2 , Kreina Sharela Vega  3 , Thomas J Ettrich  4   5 , Lorenzo Antonuzzo  8 , Lorenza Rimassa  7   17 , Sara Lonardi  6 , Lukas Perkhofer  4   5 , Teresa Macarulla  3 , Filippo Pietrantonio  1 , Andrea Casadei-Gardini  2
Affiliations
Observational Study

Ivosidenib for IDH1-Mutant Intrahepatic Cholangiocarcinoma: Insights From a Multicenter Real-World Study

Monica Niger et al. Liver Int. 2025 Sep.

Abstract

Background & aims: Cholangiocarcinoma (CCA) is a rare cancer with limited therapeutic options and a poor prognosis. While first-line combination therapies have improved outcomes, second-line treatment remains challenging. Ivosidenib, an IDH1 inhibitor, has shown promise in treating IDH1 mutant CCA, but real-world data is limited. This study aims to evaluate ivosidenib's efficacy and safety in a large cohort of patients and compare it with second-line chemotherapy.

Methods: This observational, retrospective, multicenter study included patients with advanced IDH1 mutant CCA treated with ivosidenib at 11 European institutions from May 2021 to September 2024. The primary endpoint was progression-free survival (PFS); the main secondary objectives were overall survival (OS), disease control rate (DCR), overall response rate (ORR) and safety. As a pre-planned exploratory objective, mPFS and OS of second-line ivosidenib and FOLFOX/CAPOX were compared by means of inverse probability of treatment weights (IPTW)-adjusted analysis.

Results: The study included 46 patients treated with Ivosidenib; 43.5% received ivosidenib as second line and 56.5% as ≥ third line. Median PFS and OS were 3.7 (95% CI, 2.2-36.5) and 11.5 months (95% CI, 9.5-36.5). DCR was 50.0%. Grade ≥ 3 adverse events occurred in 8.7% of patients. IPTW-adjusted mPFS was 6.9 months with ivosidenib and 2.1 months with FOLFOX/CAPOX (HR: 0.36, 95% CI, 0.20-0.64, p = 0.0005), while the mOS was 15.9 and 9.0 months with ivosidenib and FOLFOX/CAPOX, respectively (HR: 0.47, 95% CI, 0.23-0.96, p = 0.0405).

Conclusion: This study suggests that ivosidenib is a valid option for patients affected by metastatic IDH1 mutant CCA after at least one line of standard treatment.

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Conflict of interest statement

M.N. reported receiving travel expenses from AstraZeneca, speaker honoraria from Accademia della Medicina, Incyte and Servier; honoraria from Sandoz, Medpoint SRL, Incyte, AstraZeneca and Servier for editorial collaboration. Consultant honoraria from EMD Serono, Basilea Pharmaceutica, Incyte, MSD Italia, Servier, AstraZeneca and Taiho. L.R. reported receiving consulting fees from AbbVie, AstraZeneca, Basilea, Bayer, BMS, Eisai, Elevar Therapeutics, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Jazz Pharmaceuticals, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, Zymeworks; lecture fees from AstraZeneca, Bayer, BMS, Guerbet, Incyte, Ipsen, Roche, Servier; travel expenses from AstraZeneca and Servier; institutional research funding from AbbVie, Agios, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Jazz Pharmaceuticals, Lilly, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, TransThera Sciences, Zymeworks. S.L. reported receiving personal honoraria as an invited speaker from Amgen, Astra Zeneca, Bristol‐Myers Squibb, Incyte, GSK, Lilly, Merck Serono, MSD, Pierre‐Fabre, Roche and Servier; participation in an advisory board for Amgen, Astellas, Astra Zeneca, Bayer, Bristol‐Myers Squibb, Daiichi‐Sankyo, GSK, Incyte, Lilly, Merck Serono, MSD, Servier, Takeda, Rottapharm, Beigene, Fosun Pharma and Nimbus Therapeutics. F.P. reported receiving research funding (to Institution) from Lilly, BMS, Incyte, AstraZeneca, Amgen, Agenus, Rottapharm; personal honoraria as an invited speaker from BeiGene, Daiichi‐Sankyo, Seagen, Astellas, Ipsen, AstraZeneca, Servier, Bayer, Takeda, Johnson & Johnson, BMS, MSD, Amgen, Merck‐Serono, Pierre‐Fabre. Advisory/consultancy from BMS, MSD, Amgen, Pierre‐Fabre, Johnson & Johnson, Servier, Bayer, Takeda, Astellas, GSK, Daiichi‐Sankyo, Pfizer, BeiGene, Jazz Pharmaceuticals, Incyte, Rottapharm, Merck‐Serono, Italfarmaco, Gilead, AstraZeneca, Agenus. L.P. reported receiving Advisory/Consultancy from Servier, Astellas, Jazz Pharmaceuticals, AstraZeneca. THE reported receiving Advisory/Consultancy from: MSD, Roche, Sanofi, BMS, AstraZeneca, MSD, Pierre Fabre, Servier, Lilly, Ipsen, Daiichi Sankyo, Takeda. The other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Progression‐free survival (PFS) and overall survival (OS) from the start of ivosidenib treatment, regardless of treatment line.
FIGURE 2
FIGURE 2
Swimmer plot of progression‐free survival (PFS) and post‐progression survival in patients treated with ivosidenib. Each bar represents an individual patient. Green, blue, red and grey bars indicate best overall response as partial response (PR), stable disease (SD), progressive disease (PD) and not available (NA), respectively. Light red segments represent survival time following progression. Vertical bars (|) indicate patients with no progression (censored at last follow‐up), while circles (o) indicate patients who experienced progression. The symbol X denotes patients who were deceased at last follow‐up, and triangles (▲) indicate patients alive at last follow‐up.
FIGURE 3
FIGURE 3
Safety data assessment in the overall patient population.
FIGURE 4
FIGURE 4
Forest plot depicting the univariate analysis of progression‐free survival (A) and overall survival (B) according to baseline characteristics.
FIGURE 5
FIGURE 5
Comparison of second‐line outcomes between patients treated with ivosidenib and those treated with FOLFOX/CAPOX in a historical cohort. (A) Univariate analysis of progression‐free survival (PFS). (B) Univariate analysis of overall survival (OS). (C) Inverse probability of treatment weighting (IPTW)‐adjusted analysis of PFS. (D) IPTW‐adjusted analysis of OS.
See this image and copyright information in PMC

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